63 results on '"Koichi Onodera"'
Search Results
2. Exploring the mechanistic link between SF3B1 mutation and ring sideroblast formation in myelodysplastic syndrome
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Tetsuro Ochi, Tohru Fujiwara, Koya Ono, Chie Suzuki, Maika Nikaido, Daichi Inoue, Hiroki Kato, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Yukio Nakamura, and Hideo Harigae
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Medicine ,Science - Abstract
Abstract Acquired sideroblastic anemia, characterized by bone marrow ring sideroblasts (RS), is predominantly associated with myelodysplastic syndrome (MDS). Although somatic mutations in splicing factor 3b subunit 1 (SF3B1), which is involved in the RNA splicing machinery, are frequently found in MDS-RS, the detailed mechanism contributing to RS formation is unknown. To explore the mechanism, we established human umbilical cord blood-derived erythroid progenitor-2 (HUDEP-2) cells stably expressing SF3B1K700E. SF3B1K700E expressing cells showed higher proportion of RS than the control cells along with erythroid differentiation, indicating the direct contribution of mutant SF3B1 expression in erythroblasts to RS formation. In SF3B1K700E expressing cells, ABCB7 and ALAS2, known causative genes for congenital sideroblastic anemia, were downregulated. Additionally, mis-splicing of ABCB7 was observed in SF3B1K700E expressing cells. ABCB7-knockdown HUDEP-2 cells revealed an increased frequency of RS formation along with erythroid differentiation, demonstrating the direct molecular link between ABCB7 defects and RS formation. ALAS2 protein levels were obviously decreased in ABCB7-knockdown cells, indicating decreased ALAS2 translation owing to impaired Fe–S cluster export by ABCB7 defects. Finally, RNA-seq analysis of MDS clinical samples demonstrated decreased expression of ABCB7 by the SF3B1 mutation. Our findings contribute to the elucidation of the complex mechanisms of RS formation in MDS-RS.
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- 2022
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3. Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis
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Koya Ono, Tohru Fujiwara, Kei Saito, Hironari Nishizawa, Noriyuki Takahashi, Chie Suzuki, Tetsuro Ochi, Hiroki Kato, Yusho Ishii, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Rie Yamada, Yukio Nakamura, Kazuhiko Igarashi, and Hideo Harigae
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Medicine ,Science - Abstract
Abstract X-linked sideroblastic anemia (XLSA), the most common form of congenital sideroblastic anemia, is caused by a germline mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. In XLSA, defective heme biosynthesis leads to ring sideroblast formation because of excess mitochondrial iron accumulation. In this study, we introduced ALAS2 missense mutations on human umbilical cord blood-derived erythroblasts; hereafter, we refer to them as XLSA clones. XLSA clones that differentiated into mature erythroblasts showed an increased frequency of ring sideroblast formation with impaired hemoglobin biosynthesis. The expression profiling revealed significant enrichment of genes involved in ferroptosis, which is a form of regulated cell death induced by iron accumulation and lipid peroxidation. Notably, treatment with erastin, a ferroptosis inducer, caused a higher proportion of cell death in XLSA clones. XLSA clones exhibited significantly higher levels of intracellular lipid peroxides and enhanced expression of BACH1, a regulator of iron metabolism and potential accelerator of ferroptosis. In XLSA clones, BACH1 repressed genes involved in iron metabolism and glutathione synthesis. Collectively, defective heme biosynthesis in XLSA clones could confer enhanced BACH1 expression, leading to increased susceptibility to ferroptosis. The results of our study provide important information for the development of novel therapeutic targets for XLSA.
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- 2022
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4. BK Virus-Associated Urothelial Carcinoma in a Patient with Peripheral Blood Stem Cell Transplantation for Acute Lymphoblastic Leukemia: A Case Report
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Juntaro Koyama, Yoshihide Kawasaki, Shingo Kimura, Takuma Sato, Shuichi Shimada, Naoki Kawamorita, Shinichi Yamashita, Ryo Nakagawa, Akihisa Kawajiri, Koichi Onodera, Yasushi Onishi, Koji Mitsuzuka, Mika Watanabe, and Akihiro Ito
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bk virus ,bladder ,urothelial carcinoma ,hemorrhagic cystitis ,peripheral blood stem cell transplantation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Bladder tamponade due to hemorrhagic cystitis caused by BK virus in immunocompetent patients is familiar to urologists. BK virus is an important cause of nephropathy and graft loss in kidney transplant recipients. Although urothelial carcinoma of the bladder in kidney transplant recipients with persistent BK viruria is known, BK virus-associated urothelial carcinoma (BKVUC) in peripheral blood stem cell transplantation recipients is not as well known. A 54-year-old man with acute lymphoblastic leukemia was treated in the Department of Hematology of our hospital. After recurrence 25 months later, he received chemotherapy for half a year and underwent peripheral blood stem cell transplantation. He achieved temporarily complete remission, but he developed hematuria with BK virus-positive result 1 month after peripheral blood stem cell transplantation. One month later, he developed bladder tamponade-diagnosed hemorrhagic cystitis due to BK virus in our Urological Department. We performed transurethral coagulation to manage hemorrhage and removed a bleeding lesion in the bladder wall. Pathological examination of the removed bladder wall revealed pT1 stage BKVUC. We found that bladder tamponade could have led to reactivation of BK virus in this immunocompetent patient. This could be the first report of BKVUC of the bladder found in a peripheral blood stem cell transplantation recipient with close urological follow-up for 24 months. Adequate removal of bleeding lesions from the bladder mucosa with appropriate timing during hemorrhagic cystitis due to BKVUC could be essential to achieve good outcomes.
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- 2021
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5. Artificial intelligence-based technology for semi-automated segmentation of rectal cancer using high-resolution MRI.
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Atsushi Hamabe, Masayuki Ishii, Rena Kamoda, Saeko Sasuga, Koichi Okuya, Kenji Okita, Emi Akizuki, Yu Sato, Ryo Miura, Koichi Onodera, Masamitsu Hatakenaka, and Ichiro Takemasa
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Medicine ,Science - Abstract
AimAlthough MRI has a substantial role in directing treatment decisions for locally advanced rectal cancer, precise interpretation of the findings is not necessarily available at every institution. In this study, we aimed to develop artificial intelligence-based software for the segmentation of rectal cancer that can be used for staging to optimize treatment strategy and for preoperative surgical simulation.MethodImages from a total of 201 patients who underwent preoperative MRI were analyzed for training data. The resected specimen was processed in a circular shape in 103 cases. Using these datasets, ground-truth labels were prepared by annotating MR images with ground-truth segmentation labels of tumor area based on pathologically confirmed lesions. In addition, the areas of rectum and mesorectum were also labeled. An automatic segmentation algorithm was developed using a U-net deep neural network.ResultsThe developed algorithm could estimate the area of the tumor, rectum, and mesorectum. The Dice similarity coefficients between manual and automatic segmentation were 0.727, 0.930, and 0.917 for tumor, rectum, and mesorectum, respectively. The T2/T3 diagnostic sensitivity, specificity, and overall accuracy were 0.773, 0.768, and 0.771, respectively.ConclusionThis algorithm can provide objective analysis of MR images at any institution, and aid risk stratification in rectal cancer and the tailoring of individual treatments. Moreover, it can be used for surgical simulations.
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- 2022
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6. Primary adrenal extranodal NK/T-cell lymphoma: A case report and literature review
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Satoshi Ichikawa, Kei Saito, Noriko Fukuhara, Hisayuki Yokoyama, Koichi Onodera, Yasushi Onishi, Ryo Ichinohasama, and Hideo Harigae
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Primary adrenal extranodal NK/T-cell lymphoma ,l-asparaginase ,Allogeneic hematopoietic stem cell transplantation ,Graft-versus-lymphoma effect ,lymphomatous meningitis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
A 37-year-old man was admitted to our department following the detection of bulky tumors in his bilateral adrenal glands. A biopsy resulted in the diagnosis of extranodal NK/T cell lymphoma, nasal type (ENKL). After debulking by chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHCT) was performed. Relapses in the liver and adrenal glands were identified 2 months post alloHCT, for which temporary administration of l-asparaginase resulted in complete metabolic response. However, multiple relapses in the central nervous system and lethal lymphomatous meningitis successively developed. Primary adrenal ENKL could tend to present as bulky lesion and follow an aggressive clinical course.
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- 2020
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7. Laparoscopic excision of accessory spleen for recurrent autoimmune hemolytic anemia after splenectomy: a case report.
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Ryosuke Kashiwagi, Masaharu Ishida, Koichi Onodera, Shuichi Aoki, Masahiro Iseki, Takayuki Miura, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Takashi Kamei, and Michiaki Unno
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Background Splenectomy is indicated in cases of autoimmune hemolytic anemia (AIHA), which are refractory to medical management. In post-splenectomy, there exists a theoretical risk of AIHA recurrence, especially if an accessory spleen undergoes compensatory hypertrophy. In this context, we present a unique case of recurrent AIHA managed through laparoscopic excision of the accessory spleen (LEAS). Case presentation A 60-year-old male underwent laparoscopic splenectomy (LS) for AIHA refractory to standard medical therapies. Following the surgery, there was a marked improvement in hemolytic anemia symptoms, and oral steroid therapy was terminated 7 months post-LS. Nonetheless, a year after the LS, the patient exhibited a marked decline in hemoglobin levels, dropping to a concerning 5.8 g/dl, necessitating the reintroduction of oral steroids. A subsequent contrast-enhanced computed tomography (CT) scan unveiled an enlarged accessory spleen. The patient then underwent LEAS, during which the accessory spleen, obscured within adipose tissue, proved challenging to visualize laparoscopically. This obstacle was surmounted utilizing intraoperative ultrasonography (US), enabling successful excision of the accessory spleen. The post-surgical period progressed without complications, and the steroid dosage was reduced to one-twelfth of its initial preoperative quantity. Conclusions Recurrent AIHA can be instigated by post-splenectomy compensatory hypertrophy of the accessory spleen. Ensuring comprehensive splenic tissue excision is crucial in AIHA management to obviate recurrent stemming from hypertrophic remnants. In scenarios of AIHA recurrence tied to an enlarged accessory spleen, LEAS stands as a viable and efective therapeutic modality. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Safety and efficacy of tisagenlecleucel in patients with relapsed or refractory B-cell lymphoma: the first real-world evidence in Japan
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Hideki Goto, Toshio Kitawaki, Nobuharu Fujii, Koji Kato, Yasushi Onishi, Noriko Fukuhara, Takuji Yamauchi, Kazunori Toratani, Hiroki Kobayashi, Shota Yoshida, Masatoshi Shimo, Koichi Onodera, Hajime Senjo, Masahiro Onozawa, Kenji Hirata, Isao Yokota, and Takanori Teshima
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Oncology ,Surgery ,Hematology ,General Medicine - Published
- 2023
9. Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes with Donor-Specific Anti-HLA Antibodies against HLA-DP.
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Yusuke Uchibori, Koichi Onodera, Yasushi Onishi, Hiroka Komatsu, Kenta Takenaka, Yoshihiro Narumi, Tatsuya Watanabe, Hiroshi Nakamura, Kazuki Sakurai, Kazuki Hashimoto, Kyoko Inokura, Satoshi Ichikawa, Noriko Fukuhara, Hisayuki Yokoyama, and Hideo Harigae
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The presence of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) against anti-HLA-A, -B, -C, and -DRB1 in HLA-mismatched hematopoietic stem cell transplantation (HSCT) is associated with graft failure. DSAs against HLA-A, -B, -C, and -DRB1 with a mean fluorescence intensity (MFI) of greater than > 1,000 was shown to increase the risk of graft failure in single-unit umbilical cord blood transplantation (UCBT). Nevertheless, the impact of DSAs against HLA-DP or -DQ on transplantation outcomes is not fully understood. In this report, we present a case of UCBT in a patient with myelodysplastic syndrome who was positive for DSAs against HLA-DP with MFI of 1,263 before UCBT but successfully achieved neutrophil engraftment. If HLA-DP or -DQ is mismatched in UCBT, evaluating DSAs against HLA-DP or -DQ is crucial to avoid graft failure. However, the criteria for DSAs against HLA-A, -B, -C, and -DRB1 may not be directly applicable to those against HLA-DP or -DQ. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Long-Term Hemoglobin Response and Reduction in Transfusion Burden Are Maintained in Patients with Pyruvate Kinase Deficiency Treated with Mitapivat
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Rachael F. Grace, Andreas Glenthøj, Wilma Barcellini, Madeleine Verhovsek, Jennifer A. Rothman, Marta Morado, D. Mark Layton, Oliver Andres, Frédéric Galactéros, Eduard J. van Beers, Koichi Onodera, Vip Viprakasit, Satheesh Chonat, Malia P. Judge, Penelope A. Kosinski, Peter Hawkins, Sarah Gheuens, Emily Xu, Bryan McGee, Vanessa Beynon, and Hanny Al-Samkari
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
11. Aleukemic T-lymphoblastic leukemia/lymphoma with massive cerebrospinal fluid infiltration
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Satoshi Ichikawa, Noriko Fukuhara, Tsuyoshi Doman, Daichi Kiba, Yuya Tanaka, Kyoko Inokura, Naoya Morota, Koya Ono, Koichi Onodera, Yasushi Onishi, Hisayuki Yokoyama, Ryo Ichinohasama, and Hideo Harigae
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Histology ,Hematology ,Pathology and Forensic Medicine - Published
- 2022
12. TM5614, an Inhibitor of Plasminogen Activator Inhibitor-1, Exerts an Antitumor Effect on Chronic Myeloid Leukemia
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Katsuyuki, Sasaki, Tohru, Fujiwara, Tetsuro, Ochi, Koya, Ono, Hiroki, Kato, Koichi, Onodera, Satoshi, Ichikawa, Noriko, Fukuhara, Yasushi, Onishi, Hisayuki, Yokoyama, Toshio, Miyata, and Hideo, Harigae
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Furin ,Drug Resistance, Neoplasm ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Plasminogen Activator Inhibitor 1 ,Matrix Metalloproteinase 14 ,Humans ,Antineoplastic Agents ,Apoptosis ,RNA, Messenger ,General Medicine ,K562 Cells ,Protein Kinase Inhibitors ,General Biochemistry, Genetics and Molecular Biology - Abstract
Chronic myeloid leukemia (CML) is triggered by t(9;22)(q34;q11.2) translocation, leading to the formation of the BCR-ABL1 fusion gene. Although the development of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has dramatically improved the prognosis of CML, the disease could often relapse, presumably because leukemic stem cell fraction of CML (CML-LSC) may reside in specific niches, and also acquire an ability to resist the cytotoxic agents. Recently a study indicated that pharmacological inhibition of plasminogen activator inhibitor-1 (PAI-1, also known as SERPINE1) would cause detachment of CML-LSCs from their niche by inducing maturation of membrane-type matrix metalloprotease-1 (MT1-MMP), leading to increased susceptibility of CML-LSCs against TKIs. However, the direct antitumor effect of PAI-1 inhibition in CML remains unclear. Because PAI-1 mRNA expression was lower in CML cell line (K562) than bone marrow mononuclear cells derived from CML patients, we established K562 cell clones stably expressing exogenous PAI-1 (K562/PAI-1). We found that TM5614 treatment significantly suppressed cell proliferation and induced apoptosis in K562/PAI-1 cells, accompanied by increased activity of Furin protease, which is a known target of PAI-1. Besides processing mature MT1-MMP, Furin is in charge of cleaving the NOTCH receptor to form a heterodimer before exporting it to the cell surface membrane. In K562/PAI-1 cells, TM5614 treatment increased NOTCH1 intracellular domain (NICD) protein expression as well as NOTCH1 target of HEY1 mRNA levels. Finally, forced expression of either Furin or NICD in K562/PAI-1 cells significantly inhibited cell proliferation and induced apoptosis. Collectively, PAI-1 inhibition may have an antitumor effect by modulating the Furin/NICD pathway.
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- 2022
13. Elucidation of the Role of FAM210B in Mitochondrial Metabolism and Erythropoiesis
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Chie Suzuki, Tohru Fujiwara, Hiroki Shima, Koya Ono, Kei Saito, Hiroki Kato, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Yukio Nakamura, Kazuhiko Igarashi, and Hideo Harigae
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Cell Biology ,Molecular Biology ,Research Article - Abstract
Mitochondria play essential and specific roles during erythroid differentiation. Recently, FAM210B, encoding a mitochondrial inner membrane protein, has been identified as a novel target of GATA-1, as well as an erythropoietin-inducible gene. While FAM210B protein is involved in regulate mitochondrial metabolism and heme biosynthesis, its detailed function remains unknown. Here, we generated both knockout and knockdown of endogenous FAM210B in human induced pluripotent stem-derived erythroid progenitor (HiDEP) cells using CRISPR/Cas9 methodology. Intriguingly, erythroid differentiation was more pronounced in the FAM210B-depleted cells, and this resulted in increased frequency of orthochromatic erythroblasts and decreased frequencies of basophilic/polychromatic erythroblasts. Comprehensive metabolite analysis and functional analysis indicated that oxygen consumption rates and the NAD (NAD(+))/NADH ratio were significantly decreased, while lactate production was significantly increased in FAM210B deletion HiDEP cells, indicating involvement of FAM210B in mitochondrial energy metabolism in erythroblasts. Finally, we purified FAM210B-interacting protein from K562 cells that stably expressed His/biotin-tagged FAM210B. Mass spectrometry analysis of the His/biotin-purified material indicated interactions with multiple subunits of mitochondrial ATP synthases, such as subunit alpha (ATP5A) and beta (ATP5B). Our results suggested that FAM210B contributes prominently to erythroid differentiation by regulating mitochondrial energy metabolism. Our results provide insights into the pathophysiology of dysregulated hematopoiesis.
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- 2022
14. [The Evolution of the Treatment of Chronic Myelogenous Leukemia]
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Koichi, Onodera and Noriko, Fukuhara
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Imatinib Mesylate ,Fusion Proteins, bcr-abl ,Humans ,Prognosis ,Protein Kinase Inhibitors - Abstract
Chronic myelogenous leukemia(CML)is a myeloproliferative neoplasm caused by a reciprocal translocation (t 9 ; 22) (q34 ; q11). The finding that the constitutive tyrosine kinase activity of the BCR-ABL1 fusion protein, which is produced by fusing the ABL1 and BCR genes, is involved in the pathogenesis of CML has led to the development of drugs targeting the BCR-ABL1 fusion protein. Imatinib, a first-generation tyrosine kinase inhibitor(TKI), was introduced in 2001 as a treatment for CML, dramatically changing CML therapy. With the advent of imatinib, disease progression is largely prevented and the prognosis of CML patients is markedly improved, allowing a substantial proportion of patients to remain in the chronic phase for an extended period of time. In the TKI-era, it is no longer the primary disease that defines the long-term prognosis of CML patients, but rather comorbidities other than CML and adverse events(AEs), including cardiovascular events, and management to avoid AEs associated with long-term TKI use has become increasingly important. In recent years, treatment-free remission(TFR)is becoming a new therapeutic goal, as many reports have shown that some patients who have achieved deep molecular response with TKIs can maintain long-term TFR without relapsing after TKI discontinuation.
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- 2022
15. Salvage Cord Blood Transplantation for Sustained Remission of Acute Megakaryoblastic Leukemia That Relapsed Early after Myeloablative Transplantation
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Hideo Harigae, Junichi Kameoka, Noriko Fukuhara, Hisayuki Yokoyama, Yasushi Onishi, Satoshi Ichikawa, Tohru Fujiwara, Koichi Onodera, Kyoko Inokura, Kazuki Sakurai, and Kei Saito
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Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,Mediastinal germ cell tumor ,medicine.medical_treatment ,Case Report ,cord blood transplantation ,Hematopoietic stem cell transplantation ,030204 cardiovascular system & hematology ,mediastinal germ cell tumor ,03 medical and health sciences ,Acute megakaryoblastic leukemia ,0302 clinical medicine ,Refractory ,Leukemia, Megakaryoblastic, Acute ,Internal medicine ,Internal Medicine ,medicine ,Humans ,allogeneic hematopoietic stem cell transplantation ,Cord blood transplantation ,Salvage Therapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,General Medicine ,acute megakaryoblastic leukemia ,medicine.disease ,disseminated fusariosis ,Transplantation ,030211 gastroenterology & hepatology ,Cord Blood Stem Cell Transplantation ,Sustained remission ,business - Abstract
Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia accompanied by an aggressive clinical course and dismal prognosis. We herein report a case of AMKL preceded by mediastinal germ cell tumor that relapsed early after allogeneic hematopoietic stem cell transplantation with myeloablative conditioning but was successfully treated using salvage cord blood transplantation (CBT) with reduced-intensity conditioning. Although several serious complications developed, sustained remission with a favorable general condition was ultimately achieved. Although an optimal therapeutic strategy remains to be established, the graft-versus-leukemia effect of CBT may be promising, even for the treatment of refractory AMKL.
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- 2021
16. Constructing an optical fiber sensor network for natural environment remote monitoring.
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Lee See Goh, Koichi Onodera, Mitsuhisa Kanetsuna, Kazuhiro Watanabe, and Norihiko Shinomiya
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- 2011
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17. Altered Transcription By GATA1 Impairs Autophagy and Prevents Ferroptosis in X-Linked Sideroblastic Anemia
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Koya Ono, Tohru Fujiwara, Hiroki Shima, Hironari Nishizawa, Chie Suzuki, Noriyuki Takahashi, Hiroki Kato, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Yukio Nakamura, Kazuhiko Igarashi, and Hideo Harigae
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
18. MRI-detected extramural vascular invasion potentiates the risk for pathological metastasis to the lateral lymph nodes in rectal cancer
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Masamitsu Hatakenaka, Ryo Miura, Koichi Okuya, Emi Akizuki, Ichiro Takemasa, Masayuki Ishii, Takahiro Korai, Atsushi Hamabe, Kenji Okita, Koichi Onodera, and Toshihiko Nishidate
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Male ,medicine.medical_specialty ,Colorectal cancer ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Surgical oncology ,medicine ,Humans ,Neoplasm Invasiveness ,Pathological ,Univariate analysis ,medicine.diagnostic_test ,Rectal Neoplasms ,business.industry ,Magnetic resonance imaging ,General Medicine ,Prognosis ,medicine.disease ,Magnetic Resonance Imaging ,Dissection ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Lymph Node Excision ,Female ,030211 gastroenterology & hepatology ,Surgery ,Lymph ,Radiology ,business - Abstract
Multidisciplinary treatment for locally advanced rectal cancer requires an accurate assessment of the risk of metastasis to the lateral lymph nodes (LNs). We herein aimed to stratify the risk of pathological metastasis to lateral LNs based on the preoperatively detected malignant features. All patients with rectal cancer who underwent surgery from January 2016 to July 2020 were identified. We recorded the TNM factors; perirectal and lateral LN sizes; and MRI findings, including mesorectal fascia involvement, extramural vascular invasion (EMVI), tumor site, and tumor distance from the anal verge. 101 patients underwent rectal resection with lateral lymph node dissection, of whom 16 (15.8%) exhibited pathological metastases to the lateral LNs. Univariate analyses demonstrated that lateral LN metastasis was significantly correlated with mrEMVI positivity (p = 0.0023) and a baseline lateral LN short-axis length of ≥ 5 mm (p
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- 2021
19. Successful Treatment of Primary Refractory Angioimmunoblastic T-cell Lymphoma With Cord Blood Transplantation
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Yasushi Onishi, Koichi Onodera, Eijiro Furukawa, Noriko Fukuhara, Ryo Ichinohasama, Hideo Harigae, Satoshi Ichikawa, Hisayuki Yokoyama, and Kei Saito
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Cancer Research ,Pathology ,medicine.medical_specialty ,business.industry ,Hematology ,Middle Aged ,Lymphoma, T-Cell ,medicine.disease_cause ,Epstein–Barr virus ,Oncology ,medicine ,Humans ,Female ,Cord Blood Stem Cell Transplantation ,business ,Refractory Angioimmunoblastic T-cell Lymphoma ,Cord blood transplantation - Published
- 2020
20. A novel case of γδ T cell leukemia with recurrent genetic abnormalities accompanied by agranulocytosis
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Yasushi Onishi, Shunsuke Hatta, Kei Saito, Ryo Ichinohasama, Hideo Harigae, Tohru Fujiwara, Hisayuki Yokoyama, Satoshi Ichikawa, Noriko Fukuhara, Fumiyoshi Fujishima, and Koichi Onodera
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medicine.medical_specialty ,Hematology ,business.industry ,Internal medicine ,T-cell leukemia ,Immunology ,Medicine ,General Medicine ,business - Published
- 2020
21. Successful Treatment of Life-threatening Bleeding Caused by Acquired Factor X Deficiency Associated with Respiratory Infection
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Satoshi Ichikawa, Yuya Tanaka, Yasushi Onishi, Minami Fujiwara, Kei Saito, Yoonha Lee, Koichi Onodera, Hideo Harigae, Noriko Fukuhara, and Hisayuki Yokoyama
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Adult ,Male ,medicine.medical_specialty ,Case Report ,Hemorrhage ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,pneumonia ,Humans ,Factor X Deficiency ,Respiratory Tract Infections ,Coagulation Disorder ,Hematuria ,Prothrombin time ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,Autoantibody ,Respiratory infection ,General Medicine ,acquired factor X deficiency ,medicine.disease ,Pneumonia ,Coagulation ,Prothrombin Time ,030211 gastroenterology & hepatology ,Partial Thromboplastin Time ,Blood Coagulation Tests ,business ,severe hematuria ,Partial thromboplastin time - Abstract
Acquired factor X deficiency (AFXD) is a very rare coagulation disorder. A 40-year-old man with no comorbidities suffering from a fever, malaise, and severe hemorrhagic symptoms, including massive hematuria, was emergently admitted. His platelet count was normal, but his prothrombin time and activated partial thromboplastin time were markedly prolonged, which was thought to be due to autoantibody against a coagulation factor in the common pathway. Despite severe massive hematuria resulting in transient renal failure, he was successfully treated with urgent immunosuppressive therapy. Computed tomography revealed bronchopneumonia, which improved with antibiotic administration. AFXD without evidence of amyloidosis was subsequently diagnosed.
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- 2020
22. Long-term survival after cord blood transplantation for acute myeloid leukemia complicated with disseminated fusariosis
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Satoshi Ichikawa, Yasushi Onishi, Hideo Harigae, Yoko Okitsu, Noriko Fukuhara, Shotaro Watanabe, and Koichi Onodera
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0301 basic medicine ,Microbiology (medical) ,Fusariosis ,medicine.medical_specialty ,Chemotherapy ,Neutrophil Engraftment ,business.industry ,medicine.medical_treatment ,030106 microbiology ,Myeloid leukemia ,Consolidation Chemotherapy ,Hematopoietic stem cell transplantation ,Neutropenia ,medicine.disease ,Surgery ,Transplantation ,03 medical and health sciences ,surgical procedures, operative ,0302 clinical medicine ,Infectious Diseases ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,business - Abstract
Fusariosis is a critical infectious complication that can develop in immunocompromised hosts, mainly under conditions of prolonged neutropenia, and is often disseminated and associated with a high mortality rate. Disseminated fusariosis developing during the course of hematopoietic stem cell transplantation (HSCT) is a critical condition, and there have been few reports of successful treatment of cases complicated with fusariosis before HSCT. Here, we present a case of acute myeloid leukemia (AML) with the development of fungal endophthalmitis during chemotherapy. Vitrectomy was performed and Fusarium solani infection was confirmed by vitreal culture. The infection was also disseminated to the lung, triceps, and spleen. The splenic lesions disappeared with the administration of antifungal agents, and residual lesions in the lung and triceps were surgically resected. After two courses of consolidation chemotherapy, the patient received cord blood transplantation (CBT) twice because of graft failure in the first transplantation. Antifungal agents were administered continuously during chemotherapy and transplantation. Although Fusarium sinusitis developed after neutrophil engraftment, it was well controlled by surgical resection. Thereafter, the patient has been well without recurrence of fusariosis for more than 2 years since transplantation. A combination of continuous administration of antifungal agents and vigorous surgical intervention may be important for management of disseminated fusariosis in the setting of HSCT.
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- 2020
23. Successful treatment of methotrexate-associated classical Hodgkin lymphoma with brentuximab vedotin-combined chemotherapy: a case series
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Tsuyoshi Shirai, Hideo Harigae, Yasushi Onishi, Satoshi Ichikawa, Hiroshi Fujii, Hisayuki Yokoyama, Kei Saito, Noriko Fukuhara, Koichi Onodera, and Ryo Ichinohasama
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medicine.medical_specialty ,medicine.medical_treatment ,ABVD Regimen ,macromolecular substances ,Bleomycin ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,immune system diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,skin and connective tissue diseases ,Brentuximab vedotin ,Brentuximab Vedotin ,Chemotherapy ,business.industry ,food and beverages ,Combination chemotherapy ,Hematology ,medicine.disease ,Hodgkin Disease ,Regimen ,Methotrexate ,Treatment Outcome ,chemistry ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,Female ,business ,030215 immunology ,medicine.drug - Abstract
Methotrexate (MTX)-associated classical Hodgkin lymphoma (CHL) is unlikely to regress following discontinuation of MTX, and its treatment usually requires chemotherapy. Standard chemotherapy for CHL is the ABVD regimen, which contains pneumotoxic bleomycin. This can be problematic in MTX-CHL patients suffering from an autoimmune disease (AID), such as rheumatoid arthritis (RA), as they frequently have pulmonary complications. However, brentuximab vedotin (BV)-containing chemotherapy without bleomycin (A + AVD regimen) was recently reported to show favorable efficacy for CHL, and could therefore be beneficial in MTX-CHL. We treated three cases of MTX-CHL using the A + AVD regimen. All were female and had received MTX for more than 15 years. Underlying AIDs in these patients were RA in two patients, and overlap syndrome with systemic lupus erythematosus and dermatomyositis in one patient. The A + AVD regimen resulted in a complete response in all patients. Peripheral neuropathy developed in two patients, necessitating reduction of the BV dose. All three patients experienced hematological toxicity necessitating dose reduction; however, no severe adverse effects, including infection or pulmonary complication, were documented. RA was well-controlled without additional immunosuppressants. The A + AVD regimen is a promising chemotherapy for MTX-CHL with favorable efficacy and tolerable toxicity profiles.
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- 2020
24. Unrelated cord blood transplantation for adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders
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Yasushi Onishi, Koichi Onodera, Noriko Fukuhara, Hiroki Kato, Satoshi Ichikawa, Tohru Fujiwara, Hisayuki Yokoyama, Minami Yamada-Fujiwara, and Hideo Harigae
- Subjects
Adult ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Young Adult ,T-Lymphocytes ,Hematopoietic Stem Cell Transplantation ,Humans ,Hematology ,Cord Blood Stem Cell Transplantation ,Middle Aged ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Lymphoproliferative Disorders ,Retrospective Studies - Abstract
Adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders (EBV-T/NK-LPDs) often progress rapidly, and require allogeneic stem cell transplantation early in the course of treatment. Unrelated cord blood transplantation (UCBT) is a readily available option for patients without HLA-matched donors. We retrospectively analyzed the outcomes of 12 UCBT in adult patients with chronic active EBV infection (CAEBV, n = 8), EBV-positive hemophagocytic lymphohistiocytosis following primary EBV infection (n = 2), hydroa vacciniforme-like lymphoproliferative disorder (n = 1), and systemic EBV-positive T-cell lymphoma of childhood (STCLC, n = 1). The median age at transplantation was 31.5 years (range 19-58). At the median follow-up time for survivors, which was 6.3 years (range 0.3-11.3), 3-year overall survival (OS) rates in all patients and 8 CAEBV patients were 68.2% (95% CI 28.6-88.9) and 83.3% (95% CI 27.3-97.5), respectively. Graft failure occurred in 4 of 8 CAEBV patients, requiring a second UCBT to achieve neutrophil engraftment. The cumulative incidence of grade II-IV acute GVHD was 33.3% (95% CI 9.1-60.4%). The EBV-DNA load became undetectable or very low after UCBT in all cases. UCBT may be a promising treatment option for adult-onset EBV-T/NK-LPDs.
- Published
- 2021
25. Diffuse Large B-cell Lymphoma Presenting as Peritoneal Lymphomatosis: A Case Report and Literature Review
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Satoshi Ichikawa, Noriko Fukuhara, Kei Saito, Koichi Onodera, Yasushi Onishi, Hisayuki Yokoyama, Ryo Ichinohasama, and Hideo Harigae
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Biopsy, Needle ,Internal Medicine ,Humans ,Female ,General Medicine ,Lymphoma, Large B-Cell, Diffuse ,Middle Aged ,Peritoneum ,Peritoneal Neoplasms - Abstract
Peritoneal lymphomatosis (PL) is a rare presentation of malignant lymphoma cases, many of which are diagnosed as diffuse large B-cell lymphoma (DLBCL) and characterized by aggressive clinical courses. We herein report a 63-year-old woman presenting with the rapid development of abdominal distention due to bulky peritoneal tumors. The pathological evaluation of a needle biopsy sample, combined with flow cytometry, yielded the diagnosis of DLBCL. Prompt chemotherapeutic intervention resulted in favorable disease control and sustained complete remission. It is necessary to diagnose cases of DLBCL presenting as PL early to ensure prompt treatment and prevent mortality.
- Published
- 2021
26. Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis
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Koya Ono, Tohru Fujiwara, Kei Saito, Hironari Nishizawa, Noriyuki Takahashi, Chie Suzuki, Tetsuro Ochi, Hiroki Kato, Yusho Ishii, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Rie Yamada, Yukio Nakamura, Kazuhiko Igarashi, and Hideo Harigae
- Subjects
Multidisciplinary ,Erythroblasts ,Iron ,Mutation ,Ferroptosis ,Humans ,Genetic Diseases, X-Linked ,Heme ,5-Aminolevulinate Synthetase ,Anemia, Sideroblastic - Abstract
X-linked sideroblastic anemia (XLSA), the most common form of congenital sideroblastic anemia, is caused by a germline mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. In XLSA, defective heme biosynthesis leads to ring sideroblast formation because of excess mitochondrial iron accumulation. In this study, we introduced ALAS2 missense mutations on human umbilical cord blood-derived erythroblasts; hereafter, we refer to them as XLSA clones. XLSA clones that differentiated into mature erythroblasts showed an increased frequency of ring sideroblast formation with impaired hemoglobin biosynthesis. The expression profiling revealed significant enrichment of genes involved in ferroptosis, which is a form of regulated cell death induced by iron accumulation and lipid peroxidation. Notably, treatment with erastin, a ferroptosis inducer, caused a higher proportion of cell death in XLSA clones. XLSA clones exhibited significantly higher levels of intracellular lipid peroxides and enhanced expression of BACH1, a regulator of iron metabolism and potential accelerator of ferroptosis. In XLSA clones, BACH1 repressed genes involved in iron metabolism and glutathione synthesis. Collectively, defective heme biosynthesis in XLSA clones could confer enhanced BACH1 expression, leading to increased susceptibility to ferroptosis. The results of our study provide important information for the development of novel therapeutic targets for XLSA.
- Published
- 2021
27. Deep-learning algorithm to detect fibrosing interstitial lung disease on chest radiographs
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Hirotaka Nishikiori, Koji Kuronuma, Kenichi Hirota, Naoya Yama, Tomohiro Suzuki, Maki Onodera, Koichi Onodera, Kimiyuki Ikeda, Yuki Mori, Yuichiro Asai, Yuzo Takagi, Seiwa Honda, Hirofumi Ohnishi, Masamitsu Hatakenaka, Hiroki Takahashi, and Hirofumi Chiba
- Subjects
Pulmonary and Respiratory Medicine - Abstract
BackgroundAntifibrotic therapies are available to treat chronic fibrosing interstitial lung diseases (CF-ILDs), including idiopathic pulmonary fibrosis. Early use of these treatments is recommended to slow deterioration of respiratory function and to prevent acute exacerbation. However, identifying patients in the early stages of CF-ILD using chest radiographs is challenging. In this study, we developed and tested a deep-learning algorithm to detect CF-ILD using chest radiograph images.MethodFrom the image archive of Sapporo Medical University Hospital, 653 chest radiographs from 263 patients with CF-ILDs and 506 from 506 patients without CF-ILD were identified; 921 were used for deep learning and 238 were used for algorithm testing. The algorithm was designed to output a numerical score ranging from 0 to 1, representing the probability of CF-ILD. Using the testing dataset, the algorithm's capability to identify CF-ILD was compared with that of doctors. A second dataset, in which CF-ILD was confirmed using computed tomography images, was used to further evaluate the algorithm's performance.ResultsThe area under the receiver operating characteristic curve, which indicates the algorithm's detection capability, was 0.979. Using a score cut-off of 0.267, the sensitivity and specificity of detection were 0.896 and 1.000, respectively. These data showed that the algorithm's performance was noninferior to that of doctors, including pulmonologists and radiologists; performance was verified using the second dataset.ConclusionsWe developed a deep-learning algorithm to detect CF-ILDs using chest radiograph images. The algorithm's detection capability was noninferior to that of doctors.
- Published
- 2022
28. Artificial intelligence-based technology for semi-automated segmentation of rectal cancer using high-resolution MRI
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Atsushi Hamabe, Masayuki Ishii, Rena Kamoda, Saeko Sasuga, Koichi Okuya, Kenji Okita, Emi Akizuki, Yu Sato, Ryo Miura, Koichi Onodera, Masamitsu Hatakenaka, and Ichiro Takemasa
- Subjects
Technology ,Multidisciplinary ,Artificial Intelligence ,Rectal Neoplasms ,Image Processing, Computer-Assisted ,Humans ,Neural Networks, Computer ,Magnetic Resonance Imaging - Abstract
Aim Although MRI has a substantial role in directing treatment decisions for locally advanced rectal cancer, precise interpretation of the findings is not necessarily available at every institution. In this study, we aimed to develop artificial intelligence-based software for the segmentation of rectal cancer that can be used for staging to optimize treatment strategy and for preoperative surgical simulation. Method Images from a total of 201 patients who underwent preoperative MRI were analyzed for training data. The resected specimen was processed in a circular shape in 103 cases. Using these datasets, ground-truth labels were prepared by annotating MR images with ground-truth segmentation labels of tumor area based on pathologically confirmed lesions. In addition, the areas of rectum and mesorectum were also labeled. An automatic segmentation algorithm was developed using a U-net deep neural network. Results The developed algorithm could estimate the area of the tumor, rectum, and mesorectum. The Dice similarity coefficients between manual and automatic segmentation were 0.727, 0.930, and 0.917 for tumor, rectum, and mesorectum, respectively. The T2/T3 diagnostic sensitivity, specificity, and overall accuracy were 0.773, 0.768, and 0.771, respectively. Conclusion This algorithm can provide objective analysis of MR images at any institution, and aid risk stratification in rectal cancer and the tailoring of individual treatments. Moreover, it can be used for surgical simulations.
- Published
- 2021
29. T-cell receptor-silent peripheral T-cell lymphoma complicated with hemophagocytic lymphohystiocytosis
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Yasushi Onishi, Koichi Onodera, Hirofumi Watanabe, Takumi Sawada, Noriko Fukuhara, Hisayuki Yokoyama, Daigo Michimata, Eijiro Furukawa, Koya Ono, Chie Suzuki, Naoya Morota, Hideo Harigae, Satoshi Ichikawa, and Kazuki Sakurai
- Subjects
medicine.medical_specialty ,Hematology ,business.industry ,T-cell receptor ,Receptors, Antigen, T-Cell ,Lymphoma, T-Cell, Peripheral ,General Medicine ,medicine.disease ,Peripheral T-cell lymphoma ,Lymphohistiocytosis, Hemophagocytic ,Text mining ,Internal medicine ,Cancer research ,Medicine ,Humans ,business - Published
- 2021
30. High-throughput liquid chromatography/electrospray ionization-tandem mass spectrometry method using in-source collision-induced dissociation for simultaneous quantification of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in human plasma
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Kensuke Shigeta, Toshihiro Sato, Noriko Fukuhara, Koichi Onodera, Shinya Takasaki, Yasushi Onishi, Yu Sato, Masafumi Kikuchi, Tensei Hirasawa, Jiro Ogura, Masamitsu Maekawa, and Nariyasu Mano
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Male ,Spectrometry, Mass, Electrospray Ionization ,medicine.drug_class ,Clinical Biochemistry ,Dasatinib ,Mass spectrometry ,030226 pharmacology & pharmacy ,01 natural sciences ,Biochemistry ,Tyrosine-kinase inhibitor ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Tandem Mass Spectrometry ,hemic and lymphatic diseases ,Drug Discovery ,Nitriles ,medicine ,Humans ,Molecular Biology ,Protein Kinase Inhibitors ,Pharmacology ,Chromatography ,Aniline Compounds ,Leukemia ,medicine.diagnostic_test ,Adenine ,010401 analytical chemistry ,General Medicine ,Middle Aged ,0104 chemical sciences ,High-Throughput Screening Assays ,Pyrimidines ,Nilotinib ,chemistry ,Therapeutic drug monitoring ,Ibrutinib ,Imatinib Mesylate ,Quinolines ,Female ,Drug Monitoring ,Bosutinib ,Tyrosine kinase ,medicine.drug ,Chromatography, Liquid - Abstract
Recent studies have shown that therapeutic drug monitoring of tyrosine kinase inhibitors (TKIs) could improve treatment efficacy and safety. A simple analytical method using high-performance LC/electrospray ionization-tandem mass spectrometry has been developed and validated for simultaneous quantification of BCR-ABL and Bruton's TKIs used for chronic leukemia (imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib) in human plasma. Although these structures and physical properties are similar, owing to their different linear ranges, simultaneously determining the plasma levels of these five TKIs by applying optimal MS parameters remains difficult. A quantitative range exceeding 60,000-fold was required, and the linear dynamic ranges of imatinib, bosutinib, and nilotinib were limited because of the presence of a saturated detection signal. In this study, we applied the in-source collision-induced dissociation technique to control the ion amounts in mass spectrometry. This new method allowed rapid determination within 5 min with simple pretreatment. The method was validated according to the US Food and Drug Administration guidelines. Moreover, all samples of patients with chronic leukemia were successfully measured and their values were within the linear range of measurement. Therefore, our high-throughput analytical system is useful to measure the plasma concentrations of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in clinical practice.
- Published
- 2021
31. Long-term remission of primary refractory ALK-positive anaplastic large cell lymphoma after allogeneic hematopoietic stem cell transplantation.
- Author
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Masahiro Miyazaki, Satoshi Ichikawa, Yasushi Onishi, Noriko Fukuhara, Eijiro Furukawa, Koichi Onodera, Hisayuki Yokoyama, Ryo Ichinohasama, and Hideo Harigae
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- 2022
- Full Text
- View/download PDF
32. Diffuse Large B-cell Lymphoma Presenting as Peritoneal Lymphomatosis: A Case Report and Literature Review.
- Author
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Satoshi Ichikawa, Noriko Fukuhara, Kei Saito, Koichi Onodera, Yasushi Onishi, Hisayuki Yokoyama, Ryo Ichinohasama, and Hideo Harigae
- Published
- 2022
- Full Text
- View/download PDF
33. Second direct-acting antiviral therapy for hepatitis C virus infection after umbilical cord blood transplantation: A case report
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Koichi Onodera, Yasushi Onishi, Kazunori Murai, Hisayuki Yokoyama, Atsushi Masamune, Satoshi Ichikawa, Yuya Tanaka, Noriko Fukuhara, Lee Yonha, Hideo Harigae, and Jun Inoue
- Subjects
0301 basic medicine ,Microbiology (medical) ,Oncology ,medicine.medical_specialty ,Sofosbuvir ,medicine.medical_treatment ,030106 microbiology ,Hematopoietic stem cell transplantation ,Hepacivirus ,Antiviral Agents ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Umbilical Cord Blood Transplantation ,business.industry ,Ribavirin ,Hematopoietic Stem Cell Transplantation ,virus diseases ,Glecaprevir ,Hepatitis C, Chronic ,Hepatitis C ,digestive system diseases ,Pibrentasvir ,Transplantation ,surgical procedures, operative ,Infectious Diseases ,chemistry ,Drug Therapy, Combination ,Cord Blood Stem Cell Transplantation ,business ,Viral load ,medicine.drug - Abstract
Hepatitis C virus (HCV) infection has an adverse impact on outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). It is recommended that HSCT candidates infected with HCV receive the treatment prior to transplantation. Although the recent approval of direct-acting antivirals (DAAs) has led to great advances in the treatment of HCV infection, little information is available on the efficacy and safety of DAA therapy in patients receiving allogeneic HSCT. Herein, we report the clinical course of an umbilical cord blood (UCB) recipient treated with DAAs for HCV infection. The patient achieved HCV RNA negativity with glecaprevir and pibrentasvir after consolidation therapy for acute myeloid leukemia (AML), and underwent transplantation before confirming sustained virological response (SVR) at 12 weeks. The HCV viral load became detectable on day +28 after transplantation and second HCV treatment with sofosbuvir, velpatasvir, and ribavirin was required. It is important to confirm SVR prior to transplantation, but it is often difficult. If early transplantation is required, close monitoring of HCV RNA after transplantation is needed. Further investigation is required to clarify the optimal management of HCV infection for allogeneic HSCT recipients in the DAA era.
- Published
- 2020
34. Epstein-Barr virus-positive diffuse large B-cell lymphoma after sustained remission of T-cell prolymphocytic leukemia with alemtuzumab
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Yasushi Onishi, Koichi Onodera, Noriko Fukuhara, Hisayuki Yokoyama, Ryo Ichinohasama, Hideo Harigae, Satoshi Ichikawa, and Kei Saito
- Subjects
Cancer Research ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,business.industry ,T cell ,Spleen ,Hematology ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Leukemia, Prolymphocytic, T-Cell ,medicine ,Cancer research ,T-cell prolymphocytic leukemia ,Alemtuzumab ,Humans ,Bone marrow ,Lymph ,Lymphoma, Large B-Cell, Diffuse ,business ,Prolymphocytic leukemia ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
T-cell prolymphocytic leukemia (T-PLL) is a rare but aggressive lymphoid neoplasm of mature post-thymic T cell phenotype, involving the peripheral blood, bone marrow, lymph nodes, liver, spleen, an...
- Published
- 2020
35. Are ADC histogram metrics repeatable?
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Koichi, Onodera, Naoya, Yama, Maki, Onodera, Naomi, Koyama, Yoshifusa, Kyuna, Mitsuhiro, Nakanishi, and Masamitsu, Hatakenaka
- Subjects
body regions ,ADC ,DWI ,repeatability ,histogram - Abstract
Purpose: The present study evaluated the repeatability of apparent diffusion coefficient (ADC) histogram metrics in clinical MRI.Methods: Twelve patients who underwent head MRI in our hospital from May to July in 2016 were included in the present study. All patients gave informed consent. Two sequential diffusion-weighted images with echo planar imaging (DWI-EPI) in the identical positioning were obtained. The b-factors of 0 and 1000 or 1500 s/mm2 were used, three orthogonal motion proving gradients (MPGs) were applied, and synthesized images were generated. The regions of interest (ROIs) were ssigned at the lesions on the 1st DWI and pasted onto the 2nd at the same size and location. Voxel-wise ADC was calculated by fitting the signal intensity change of each voxel into a mono-exponential curve. ADCs calculated from 1st and 2nd DWI were defined as ADC-1st and ADC-2nd, respectively. To investigate the repeatability of voxel-wise ADC in each lesion, ADC-1st and ADC-2nd were compared using Wilcoxon matched-pairs signed rank test and linear regression. To onsider repeatability of ADC histogram metrics for all lesions, minimal, 25%, median, 75%, maximum, mean, skewness, and kurtosis of ADC-1st and ADC-2nd for each lesion were compared using linear regression and Bland-Altman plot.Results: For repeatability of voxel-wise ADC, significant differences were observed between ADC-1st and ADC-2nd in 5 lesions. Linear regression did not show significance of the slope in 5 lesions. As for repeatability of ADC histogram metrics, all ADC histogram metrics except skewness and kurtosis showed significance of the slope in linear regression (p
- Published
- 2017
36. Sustained remission of giant pancreatic plasmacytoma with daratumumab
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Satoshi Ichikawa, Noriko Fukuhara, Hideo Harigae, Ryo Ichinohasama, Kei Saito, Hisayuki Yokoyama, Eijiro Furukawa, Koichi Onodera, and Yasushi Onishi
- Subjects
Oncology ,medicine.medical_specialty ,Hematology ,business.industry ,Internal medicine ,medicine ,Daratumumab ,Plasmacytoma ,General Medicine ,Sustained remission ,business ,medicine.disease - Published
- 2020
37. Repeatability analysis of ADC histogram metrics of the uterus
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Tsuyoshi Saito, Taro Takahara, Masamitsu Hatakenaka, Maki Onodera, Koichi Onodera, Thomas C. Kwee, Naoya Yama, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
- Subjects
Adult ,Uterine Cervical Neoplasms ,Cervix Uteri ,perfusion ,030218 nuclear medicine & medical imaging ,QUANTITATIVE IMAGING BIOMARKERS ,Endometrium ,03 medical and health sciences ,0302 clinical medicine ,INCOHERENT MOTION PARAMETERS ,Histogram ,REPRODUCIBILITY ,MAPS ,Humans ,Medicine ,Effective diffusion coefficient ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,repeatability ,Aged ,Aged, 80 and over ,Reproducibility ,Radiological and Ultrasound Technology ,business.industry ,MR diffusion ,LYMPHOVASCULAR INVASION ,Uterus ,Reproducibility of Results ,Pattern recognition ,General Medicine ,Repeatability ,Middle Aged ,ENDOMETRIAL CANCER ,Endometrial Neoplasms ,body regions ,Diffusion Magnetic Resonance Imaging ,030220 oncology & carcinogenesis ,Endometrial Hyperplasia ,Female ,Artificial intelligence ,APPARENT-DIFFUSION-COEFFICIENT ,Mr diffusion ,business ,histogram ,MRI - Abstract
Background Recently, histogram analysis based on voxel-wise apparent diffusion coefficient (ADC) value distribution has been increasingly performed. However, few studies have been reported regarding its repeatability. Purpose To evaluate the repeatability of ADC histogram metrics of the uterus in clinical magnetic resonance imaging (MRI). Material and Methods Thirty-three female patients who underwent pelvic MRI including diffusion-weighted imaging (DWI) were prospectively included after providing informed consent. Two sequential DWI acquisitions with identical parameters and position were obtained. Regions of interest (ROIs) for histologically confirmed uterine lesions (five cervical and three endometrial cancers, and one endometrial hyperplasia) and normal appearing tissues (21 endometrium and 33 myometrium) were assigned on the first DWI dataset and then pasted onto the second DWI dataset. ADC histogram metrics within the ROIs were calculated and repeatability was evaluated by calculating within-subject coefficient of variance (%) (wCV (%)) and Bland–Altman plot (%). Results ADC 10%, 25%, median, 75%, 90%, maximum, mean, and entropy showed high repeatability (wCV (%) Conclusion ADC histogram metrics like ADC 10%, 25%, median, 75%, 90%, maximum, mean, and entropy are robust biomarkers and could be applicable to clinical use. However, ADC skewness and kurtosis lack robustness. Radiologists should keep these characteristics and limitations in mind when interpreting quantitative DWI.
- Published
- 2019
38. Preemptive therapy for cytomegalovirus reactivation after daratumumab-containing treatment in patients with relapsed and refractory multiple myeloma
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Satoshi Ichikawa, Yasushi Onishi, Kei Saito, Akihisa Kawajiri, Ryo Nakagawa, Sayaka Sano, Noriko Fukuhara, Hideo Harigae, Koichi Onodera, Tohru Fujiwara, and Eijiro Furukawa
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Cytomegalovirus reactivation ,Cytomegalovirus ,Antiviral Agents ,Dexamethasone ,Immunocompromised Host ,Antineoplastic Agents, Immunological ,Recurrence ,Internal medicine ,Medicine ,Humans ,Valganciclovir ,In patient ,Lymphocytes ,Ganciclovir ,Lenalidomide ,Aged ,Retrospective Studies ,Hematology ,Membrane Glycoproteins ,business.industry ,Daratumumab ,Antibodies, Monoclonal ,Refractory Multiple Myeloma ,General Medicine ,Middle Aged ,ADP-ribosyl Cyclase 1 ,Cytomegalovirus Infections ,Drug Evaluation ,Female ,Virus Activation ,business ,Multiple Myeloma - Published
- 2018
39. Salvage Cord Blood Transplantation for Sustained Remission of Acute Megakaryoblastic Leukemia That Relapsed Early after Myeloablative Transplantation.
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Satoshi Ichikawa, Tohru Fujiwara, Kei Saito, Kazuki Sakurai, Kyoko Inokura, Noriko Fukuhara, Hisayuki Yokoyama, Koichi Onodera, Yasushi Onishi, Junichi Kameoka, and Hideo Harigae
- Published
- 2021
- Full Text
- View/download PDF
40. Primary adrenal extranodal NK/T-cell lymphoma: A case report and literature review
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Yasushi Onishi, Noriko Fukuhara, Koichi Onodera, Hideo Harigae, Ryo Ichinohasama, Satoshi Ichikawa, Kei Saito, and Hisayuki Yokoyama
- Subjects
Pathology ,medicine.medical_specialty ,l-asparaginase ,medicine.medical_treatment ,Central nervous system ,Hematopoietic stem cell transplantation ,Lymphomatous meningitis ,Primary adrenal extranodal NK/T-cell lymphoma ,lcsh:RC254-282 ,Article ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Biopsy ,medicine ,T-cell lymphoma ,lymphomatous meningitis ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,Hematology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Debulking ,medicine.disease ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Allogeneic hematopoietic stem cell transplantation ,medicine.symptom ,business ,Graft-versus-lymphoma effect ,030215 immunology - Abstract
A 37-year-old man was admitted to our department following the detection of bulky tumors in his bilateral adrenal glands. A biopsy resulted in the diagnosis of extranodal NK/T cell lymphoma, nasal type (ENKL). After debulking by chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHCT) was performed. Relapses in the liver and adrenal glands were identified 2 months post alloHCT, for which temporary administration of l-asparaginase resulted in complete metabolic response. However, multiple relapses in the central nervous system and lethal lymphomatous meningitis successively developed. Primary adrenal ENKL could tend to present as bulky lesion and follow an aggressive clinical course.
- Published
- 2020
41. Establishment of a Screening System to Identify Novel GATA-2 Transcriptional Regulators
- Author
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Noriko Fukuhara, K. Ohashi, Yoko Okitsu, Tohru Fujiwara, Hideo Harigae, Yasushi Onishi, Yo Saito, Masahiro Kobayashi, Koichi Onodera, and Satoshi Ichikawa
- Subjects
0301 basic medicine ,Transcription, Genetic ,Repressor ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Cell Line, Tumor ,Humans ,Genetic Testing ,Progenitor cell ,Luciferases ,Promoter Regions, Genetic ,Base Pairing ,Cell growth ,Immune Sera ,GATA2 ,General Medicine ,Dendritic cell ,Dendritic Cells ,Cell biology ,Clone Cells ,GATA2 Transcription Factor ,Haematopoiesis ,030104 developmental biology ,Gene Expression Regulation ,Cell culture ,Stem cell ,Biomarkers - Abstract
Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is essential for cell proliferation and differentiation. Heterozygous germline GATA2 mutations induce GATA-2 deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia and acute myeloid leukemia, and a profoundly reduced dendritic cell (DC) population, which is associated with increased susceptibility to viral infections. Because patients with GATA-2 deficiency syndrome could retain a wild-type copy of GATA-2, boosting residual wild-type GATA-2 activity may represent a novel therapeutic strategy for the disease. Here, we sought to establish a screening system to identify GATA-2 activators using human U937 monocytic cells as a potential model of the DC progenitor. Enforced GATA-2 expression in U937 cells induces CD205 expression, a marker of DC differentiation, indicating U937 cells as a surrogate of human primary DC progenitors. Transient luciferase reporter assays in U937 cells reveals a high promoter activity of the -0.5 kb GATA-2 hematopoietic-specific promoter (1S promoter) fused with two tandemly connected GATA-2 +9.9 kb intronic enhancers. We thus established U937-derived cell lines stably expressing tandem +9.9 kb/-0.5 kb 1S-luciferase. Importantly, forced GATA-1 expression, a repressor for GATA-2 expression, in the stable clones caused significant decreases in the luciferase activities. In conclusion, our system represents a potential tool for identifying novel regulators of GATA-2, thereby contributing to the development of novel therapeutic approaches.
- Published
- 2018
42. Hyperferritinemia after adult allogeneic hematopoietic cell transplantation: quantification of iron burden by determining non-transferrin-bound iron
- Author
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Katsunori Sasaki, Emi Yokohata, Koichi Onodera, Sonoko Kamoshita, Shokichi Tsukamoto, Nobuhiko Imahashi, Aika Seto, Koichi Miyamura, Yukiyasu Ozawa, Yoshihiro Inamoto, Masafumi Ito, Katsuya Ikuta, Daisuke Koyama, Yutaka Kohgo, Keisuke Watanabe, and Tatsunori Goto
- Subjects
Adult ,Male ,medicine.medical_specialty ,Iron Overload ,Adolescent ,Iron ,Gastroenterology ,Young Adult ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Aged ,chemistry.chemical_classification ,Hematology ,biology ,Surrogate endpoint ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,medicine.disease ,Hematologic Diseases ,Magnetic Resonance Imaging ,Ferritin ,Transplantation ,Red blood cell ,Treatment Outcome ,medicine.anatomical_structure ,Liver ,chemistry ,Transferrin ,Ferritins ,Immunology ,biology.protein ,Female ,Complication - Abstract
Iron overload is a common complication in allogeneic hematopoietic cell transplantation (HCT). We studied the prevalence of iron overload using serum ferritin from 122 allogeneic HCT survivors who had survived a median of 1259 (range 134–4261) days. We also quantified iron overload by determining non-transferrin-bound iron (NTBI), which reflects iron overload more directly than ferritin, and compared the results with those of the ferritin assay. Fifty-two patients (43 %) showed hyperferritinemia (HF) (serum ferritin >1000 ng/mL), and there was a moderate correlation between serum ferritin and the number of transfused red blood cell units (ρ = 0.71). In multivariate analyses, HF was a significant risk factor for liver dysfunction (P = 0.0001) and diabetes (P = 0.02), and was related to a lesser extent with performance status (P = 0.08). There was a significant correlation between serum ferritin and NTBI (ρ = 0.59); however, the association of NTBI with these outcomes was weaker than that of serum ferritin. In conclusion, serum ferritin is a good surrogate marker of iron overload after allogeneic HCT, and reflects organ damage more accurately than NTBI.
- Published
- 2012
43. Autoimmune-like hepatitis after allogeneic hematopoietic stem cell transplantation: humoral hepatic GvHD
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Keisuke Watanabe, Aika Seto, Takuhiro Yamaguchi, Masafumi Ito, M Doisaki, K Miyamura, Koichi Onodera, Daisuke Koyama, E. Yokohata, Tatsunori Goto, Yukiyasu Ozawa, and K Watakabe
- Subjects
Adult ,Male ,genetic structures ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Hepatitis ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,immune system diseases ,Medicine ,Humans ,Transplantation, Homologous ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,eye diseases ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Immunology ,Female ,sense organs ,business ,030215 immunology - Abstract
Autoimmune-like hepatitis after allogeneic hematopoietic stem cell transplantation: humoral hepatic GvHD
- Published
- 2016
44. Clinical significance of hemophagocytosis in BM clot sections during the peri-engraftment period following allogeneic hematopoietic SCT
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Shokichi Tsukamoto, Takahiko Yasuda, Daisuke Koyama, Mayumi Imahashi, Satoshi Nishiwaki, Yoshihiro Inamoto, Aika Seto, Keisuke Watanabe, Masafumi Ito, Tatsunori Goto, Yukiyasu Ozawa, Koichi Onodera, Nobuhiko Imahashi, and K Miyamura
- Subjects
Adult ,medicine.medical_specialty ,Pathology ,Transplantation Conditioning ,Adolescent ,Hematopoietic System ,Gastroenterology ,Phagocytosis ,Recurrence ,Internal medicine ,Humans ,Transplantation, Homologous ,Medicine ,Clinical significance ,Transplantation ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Microangiopathy ,Hematopoietic Stem Cell Transplantation ,Hematology ,Macrophage Activation ,Middle Aged ,medicine.disease ,Confidence interval ,Haematopoiesis ,Treatment Outcome ,Acute Disease ,Multivariate Analysis ,Hemophagocytosis ,Complication ,business - Abstract
The effects of macrophage activation on the outcome of allogeneic hematopoietic SCT (allo-HSCT) have yet to be fully examined. A total of 70 adult patients who received a first allo-HSCT for hematological diseases were studied. We counted the number of hemophagocytic cells in BM clot sections on day +14±7, and analyzed its impact on subsequent outcome. In all, 23 patients were diagnosed as having increased numbers of hemophagocytic cells (HP group), whereas 47 were not (non-HP group). The HP group was not associated with an increased incidence of acute or chronic GVHD, but was associated with worse hematopoietic recovery than the non-HP group. The 2-year OS for the HP group and the non-HP group was 30 and 65% (P
- Published
- 2011
45. Successful treatment with allogeneic stem cell transplantation followed by DLI and TKIs for e6a2 BCR-ABL-positive acute myeloid leukaemia
- Author
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Koichi Onodera, Isamu Sugiura, Naomi Kawashima, Satomi Yamamoto, Tatsunori Goto, Satoshi Nishiwaki, Yoshiki Akatsuka, Koichi Miyamura, Shingo Okuno, Takahiko Sato, Sonoko Kamoshita, Aika Seto, Takumi Sugimoto, Yukiyasu Ozawa, Yasuhiko Harada, and Toshihiro Iwasaki
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Neoplasm, Residual ,medicine.medical_treatment ,Fusion Proteins, bcr-abl ,Graft vs Leukemia Effect ,donor lymphocyte infusion ,Hematopoietic stem cell transplantation ,Philadelphia chromosome ,Donor lymphocyte infusion ,03 medical and health sciences ,tyrosine kinase inhibitor ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Philadelphia Chromosome ,Clinical Case Report ,BCR-ABL fusion gene ,breakpoint ,Acute leukemia ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,General Medicine ,Middle Aged ,Protein-Tyrosine Kinases ,medicine.disease ,Minimal residual disease ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,030104 developmental biology ,Lymphocyte Transfusion ,030220 oncology & carcinogenesis ,Female ,business ,Research Article - Abstract
Rationale: Patients with the e6a2 BCR-ABL transcript, 1 of the atypical transcripts, have been reported to have a poor prognosis, and allogeneic stem cell transplantation (ASCT) can be considered as additional therapy. However, long-term survival after ASCT for this disease is rare. Patient concerns: This report concerns a 55-year-old female patient with e6a2 BCR-ABL-positive acute myeloid leukemia including the outcome of ASCT followed by donor lymphocyte infusion (DLI). Diagnoses: The breakpoint was confirmed by direct sequencing. Her minimal residual disease could be detected by nested reverse-transcription polymerase chain reaction using primers for the minor BCR-ABL (e1a2) transcript. Interventions: Treatment with tyrosine kinase inhibitors (TKIs) and ASCT followed by DLI. Outcomes: Despite multiple cytogenetic and molecular relapses after ASCT, she remains in molecular remission at 46 months after ASCT. Lessons: This case indicates the efficacy of the combination of the graft-versus-leukemia effect and TKIs for e6a2 BCR-ABL-positive acute leukemia. When the Philadelphia chromosome with an unusual chromosomal breakpoint is suggested, we should clarify the breakpoint because that information can aid molecular assessments and decisions to provide an additional or alternative therapy.
- Published
- 2017
46. A NEW SUBSPACE IDENTIFICATION METHOD FOR CLOSED-LOOP SYSTEMS
- Author
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S. Joe Qin, Koichi Onodera, and Genichi Emoto
- Subjects
Identification (information) ,Observer (quantum physics) ,Markov chain ,Control theory ,General Medicine ,Kalman filter ,Canonical correlation ,Eigensystem realization algorithm ,Algorithm ,Hankel matrix ,Subspace topology ,Mathematics - Abstract
In this paper we present a new subspace identification method applicable to closed-loop data. First, Kalman predictor Markov parameters in a framework of ARX modeling with high order are obtained. These parameters are made available for subspace identification to help the estimation of the Hankel matrix which consists of the estimated predictor Markov parameters. To estimate the observer matrices, eigensystem realization algorithm (ERA) with weightings related to canonical correlation analysis (CCA) is applied to the Hankel matrix. System matrices are easily derived from the estimated observer matrices. We then demonstrate the effectiveness of the proposed algorithm via simulated and industrial closed loop data.
- Published
- 2006
47. Establishment of a Screening System to Identify Novel GATA-2 Transcriptional Regulators.
- Author
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Keiichi Ohashi, Tohru Fujiwara, Koichi Onodera, Yo Saito, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, and Hideo Harigae
- Abstract
Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is essential for cell proliferation and differentiation. Heterozygous germline GATA2 mutations induce GATA-2 deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia and acute myeloid leukemia, and a profoundly reduced dendritic cell (DC) population, which is associated with increased susceptibility to viral infections. Because patients with GATA-2 deficiency syndrome could retain a wild-type copy of GATA-2, boosting residual wild-type GATA-2 activity may represent a novel therapeutic strategy for the disease. Here, we sought to establish a screening system to identify GATA-2 activators using human U937 monocytic cells as a potential model of the DC progenitor. Enforced GATA-2 expression in U937 cells induces CD205 expression, a marker of DC differentiation, indicating U937 cells as a surrogate of human primary DC progenitors. Transient luciferase reporter assays in U937 cells reveals a high promoter activity of the -0.5 kb GATA-2 hematopoietic-specific promoter (1S promoter) fused with two tandemly connected GATA-2 +9.9 kb intronic enhancers. We thus established U937-derived cell lines stably expressing tandem +9.9 kb/-0.5 kb 1S-luciferase. Importantly, forced GATA-1 expression, a repressor for GATA-2 expression, in the stable clones caused significant decreases in the luciferase activities. In conclusion, our system represents a potential tool for identifying novel regulators of GATA-2, thereby contributing to the development of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
48. Successful treatment with allogeneic stem cell transplantation followed by DLI and TKIs for e6a2 BCR-ABL-positive acute myeloid leukaemia: A case report and literature review.
- Author
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Yasuhiko Harada, Satoshi Nishiwaki, Takumi Sugimoto, Koichi Onodera, Tatsunori Goto, Takahiko Sato, Sonoko Kamoshita, Naomi Kawashima, Aika Seto, Shingo Okuno, Satomi Yamamoto, Toshihiro Iwasaki, Yukiyasu Ozawa, Koichi Miyamura, Yoshiki Akatsuka, Isamu Sugiura, Harada, Yasuhiko, Nishiwaki, Satoshi, Sugimoto, Takumi, and Onodera, Koichi
- Published
- 2017
- Full Text
- View/download PDF
49. 879nm-LD-pumped Nd:GdVO4 laser and its thermal property
- Author
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H. Sagae, Yoshiharu Urata, Mikio Higuchi, Hiroshi Machida, Satoshi Wada, Takayo Ogawa, Koichi Onodera, and Kohei Kodaira
- Subjects
Materials science ,Dye laser ,business.industry ,Far-infrared laser ,Ti:sapphire laser ,Laser pumping ,Laser ,Vertical-cavity surface-emitting laser ,law.invention ,Optics ,law ,Diode-pumped solid-state laser ,Optoelectronics ,Laser power scaling ,business - Abstract
An 879nm-LD-pumped Nd:GdVO4 laser with a maximum slope efficiency of 78% was realized. Optical-optical conversion efficiency reached 70%. We also measured the thermal conductivity and the thermal lens effect to characterize the thermal property of the Nd:GdVO4 laser.
- Published
- 2004
50. GATA2 regulates dendritic cell differentiation.
- Author
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Koichi Onodera, Tohru Fujiwara, Yasushi Onishi, Ari Itoh-Nakadai, Yoko Okitsu, Noriko Fukuhara, Kenichi Ishizawa, Ritsuko Shimizu, Masayuki Yamamoto, and Hideo Harigae
- Subjects
- *
DENDRITIC cells , *GATA proteins , *MYELOID leukemia , *ANTIGEN presenting cells , *LYMPHOID tissue , *CELL differentiation , *BONE marrow diseases - Abstract
Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockoutand haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Lin-Sca-1+Kit+ cells, common myeloid-restricted progenitors, and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 1190. These results suggest that GATA2 plays an important role in cell-fate specification toward the myeloid vs T-lymphocyte lineage by regulating lineage-specific transcription factors in DC progenitors, thereby contributing to DC differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
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