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5. Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study

Author

Dupuis, Jehan, Bachy, Emmanuel, Morschhauser, Franck, Cartron, Guillaume, Fukuhara, Noriko, Daguindau, Nicolas, Casasnovas, René-Olivier, Snauwaert, Sylvia, Gressin, Remy, Fox, Christopher P, d’Amore, Francesco Annibale, Staber, Philipp B, Tournilhac, Olivier, Bouabdallah, Krimo, Thieblemont, Catherine, André, Marc, Rai, Shinya, Ennishi, Daisuke, Gkasiamis, Argyrios, Nishio, Mitsufumi, Fornecker, Luc-Matthieu, Delfau-Larue, Marie-Helene, Sako, Nouhoum, Mule, Sebastien, de Leval, Laurence, Gaulard, Philippe, Tsukasaki, Kunihiro, and Lemonnier, François

Published
2024
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7. Long-term outcomes of patients with primary intestinal follicular lymphoma managed with watch-and-wait strategy

Author

Iwamuro, Masaya, Tanaka, Takehiro, Ennishi, Daisuke, Matsueda, Kazuhiro, Yoshioka, Masao, Miyahara, Koji, Sakaguchi, Chihiro, Nishimura, Mamoru, Nagahara, Teruya, Mannami, Tomohiko, Takenaka, Ryuta, Oka, Shohei, Inoue, Masafumi, Takimoto, Hidetaka, Inaba, Tomoki, Kobayashi, Sayo, Toyokawa, Tatsuya, Tsugeno, Hirofumi, Suzuki, Seiyuu, Sawada, Sachiko, Tanaka, Shouichi, Tsuzuki, Takao, and Okada, Hiroyuki

Published
2023
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9. Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study

Author

Urata, Tomohiro, Naoi, Yusuke, Jiang, Aixiang, Boyle, Merrill, Sunami, Kazutaka, Imai, Toshi, Nawa, Yuichiro, Hiramatsu, Yasushi, Yamamoto, Kazuhiko, Fujii, Soichiro, Yoshida, Isao, Yano, Tomofumi, Chijimatsu, Ryota, Murakami, Hiroyuki, Ikeuchi, Kazuhiro, Kobayashi, Hiroki, Tani, Katsuma, Ujiie, Hideki, Inoue, Hirofumi, Tomida, Shuta, Yamamoto, Akira, Kondo, Takumi, Fujiwara, Hideaki, Asada, Noboru, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Matsuoka, Ken-ichi, Sawada, Keisuke, Momose, Shuji, Tamaru, Jun-ichi, Nishikori, Asami, Sato, Yasuharu, Yoshino, Tadashi, Maeda, Yoshinobu, Scott, David W., and Ennishi, Daisuke

Published
2023
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15. Establishment of a reference single-cell RNA sequencing dataset for human pancreatic adenocarcinoma

Author

Chijimatsu, Ryota, Kobayashi, Shogo, Takeda, Yu, Kitakaze, Masatoshi, Tatekawa, Shotaro, Arao, Yasuko, Nakayama, Mika, Tachibana, Naohiro, Saito, Taku, Ennishi, Daisuke, Tomida, Shuta, Sasaki, Kazuki, Yamada, Daisaku, Tomimaru, Yoshito, Takahashi, Hidenori, Okuzaki, Daisuke, Motooka, Daisuke, Ohshiro, Takahito, Taniguchi, Masateru, Suzuki, Yutaka, Ogawa, Kazuhiko, Mori, Masaki, Doki, Yuichiro, Eguchi, Hidetoshi, and Ishii, Hideshi

Published
2022
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16. Combination of reduced post‐transplant cyclophosphamide and early tacrolimus initiation increases the incidence of chronic graft‐versus‐host disease in human leukocyte antigen‐haploidentical peripheral blood stem‐cell transplantation

Author

Terao, Toshiki, Kondo, Takumi, Nakamura, Makoto, Takasuka, Hiroki, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Maeda, Yoshinobu, and Matsuoka, Ken‐ichi

Published
2024
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17. Recent updates on treatment options for primary follicular lymphoma of the gastrointestinal tract.

Author

Iwamuro, Masaya, Tanaka, Takehiro, Ennishi, Daisuke, and Otsuka, Motoyuki

Subjects
FOLLICULAR lymphoma, BOWEL obstructions, GASTROINTESTINAL system, INTESTINAL tumors, LYMPHOMAS
Abstract

Background: Primary gastrointestinal follicular lymphoma is a subtype of follicular lymphoma that originates directly from the gastrointestinal tract. Pathologically, it exhibits substantial similarities with the secondary gastrointestinal involvement observed in nodal follicular lymphoma. However, primary gastrointestinal follicular lymphoma presents clinically distinct features, necessitating divergent considerations in treatment selection compared with nodal follicular lymphoma. Areas covered: This narrative review focused on recent articles (2018–2023) regarding the long-term prognosis and treatment options for gastrointestinal follicular lymphoma. In addition, a brief overview of gastrointestinal follicular lymphomas is provided. Expert opinion: Patients with primary gastrointestinal follicular lymphoma often present with a low tumor burden. Lymphoma lesions typically remain asymptomatic for several years or may undergo spontaneous regression without immediate treatment. Therefore, a 'watch and wait' approach is justified. Conversely, when large tumor masses are identified in the gastrointestinal tract, the potential for tumor bleeding or intestinal obstruction requires timely therapeutic interventions. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Transformation to diffuse large B-cell lymphoma with germinal center B-cell like subtype and discordant light chain expression in a patient with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma

Author

Kobayashi, Hiroki, Asada, Noboru, Egusa, Yuria, Ikeda, Tomoka, Sakamoto, Misa, Abe, Masaya, Ennishi, Daisuke, Sakata, Masahiro, Takaki, Akinobu, Kawahara, Soichiro, Meguri, Yusuke, Nishimori, Hisakazu, Fujii, Nobuharu, Matsuoka, Ken-ichi, Sato, Yasuharu, Yoshino, Tadashi, and Maeda, Yoshinobu

Published
2021
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22. Collection efficiency and safety of large‐volume leukapheresis for the manufacturing of tisagenlecleucel.

Author

Kitamura, Wataru, Urata, Tomohiro, Fujii, Keiko, Fukumi, Takuya, Ikeuchi, Kazuhiro, Seike, Keisuke, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Matsuoka, Ken‐ichi, Otsuka, Fumio, Maeda, Yoshinobu, and Fujii, Nobuharu

Subjects
LEUKAPHERESIS, B cell lymphoma, BLOOD volume, CD3 antigen
Abstract

Background: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non‐Hodgkin lymphoma (r/r B‐ALL/B‐NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal‐volume leukapheresis (NVL). Large‐volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa‐cel) remain unclear. This study aimed to investigate the tolerability of LVL. Study Design and Methods: We retrospectively collected data on LVL (≥3‐fold TBV) and NVL (<3‐fold TBV) performed for patients with r/r B‐ALL/B‐NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. Results: Although pre‐apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/μL, p <.01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out‐of‐specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p =.43) and no patient discontinued leukapheresis due to any complications. Conclusion: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa‐cel. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): a multicentre, single-arm, phase 2 trial

Author

Shimada, Kazuyuki, Yamaguchi, Motoko, Atsuta, Yoshiko, Matsue, Kosei, Sato, Keijiro, Kusumoto, Shigeru, Nagai, Hirokazu, Takizawa, Jun, Fukuhara, Noriko, Nagafuji, Koji, Miyazaki, Kana, Ohtsuka, Eiichi, Okamoto, Masataka, Sugita, Yasumasa, Uchida, Toshiki, Kayukawa, Satoshi, Wake, Atsushi, Ennishi, Daisuke, Kondo, Yukio, Izumi, Tohru, Kin, Yoshihiro, Tsukasaki, Kunihiro, Hashimoto, Daigo, Yuge, Masaaki, Yanagisawa, Atsumi, Kuwatsuka, Yachiyo, Shimada, Satoko, Masaki, Yasufumi, Niitsu, Nozomi, Kiyoi, Hitoshi, Suzuki, Ritsuro, Tokunaga, Takashi, Nakamura, Shigeo, and Kinoshita, Tomohiro

Published
2020
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27. Author Correction: 5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy

Author

Sando, Yasuhisa, Matsuoka, Ken-ichi, Sumii, Yuichi, Kondo, Takumi, Ikegawa, Shuntaro, Sugiura, Hiroyuki, Nakamura, Makoto, Iwamoto, Miki, Meguri, Yusuke, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Utsunomiya, Atae, Oka, Takashi, and Maeda, Yoshinobu

Published
2021
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29. TMEM30A loss-of-function mutations drive lymphomagenesis and confer therapeutically exploitable vulnerability in B-cell lymphoma

Author

Ennishi, Daisuke, Healy, Shannon, Bashashati, Ali, Saberi, Saeed, Hother, Christoffer, Mottok, Anja, and Chan, Fong Chun

Subjects
Lymphomas -- Genetic aspects -- Care and treatment -- Patient outcomes, B cells -- Health aspects -- Genetic aspects, Membrane proteins -- Health aspects -- Genetic aspects, Biological sciences, Health
Abstract

Transmembrane protein 30A (TMEM30A) maintains the asymmetric distribution of phosphatidylserine, an integral component of the cell membrane and 'eat-me' signal recognized by macrophages. Integrative genomic and transcriptomic analysis of diffuse large B-cell lymphoma (DLBCL) from the British Columbia population-based registry uncovered recurrent biallelic TMEM30A loss-of-function mutations, which were associated with a favorable outcome and uniquely observed in DLBCL. Using TMEM30A-knockout systems, increased accumulation of chemotherapy drugs was observed in TMEM30A-knockout cell lines and TMEM30A-mutated primary cells, explaining the improved treatment outcome. Furthermore, we found increased tumor-associated macrophages and an enhanced effect of anti-CD47 blockade limiting tumor growth in TMEM30A-knockout models. By contrast, we show that TMEM30A loss-of-function increases B-cell signaling following antigen stimulation--a mechanism conferring selective advantage during B-cell lymphoma development. Our data highlight a multifaceted role for TMEM30A in B-cell lymphomagenesis, and characterize intrinsic and extrinsic vulnerabilities of cancer cells that can be therapeutically exploited. Integrative analysis in patients with diffuse large B-cell lymphoma uncovers that biallelic mutations on TMEM30A are associated with a favorable outcome and enhanced sensitivity to CD47 blockade., Author(s): Daisuke Ennishi [sup.1] [sup.2] , Shannon Healy [sup.1] , Ali Bashashati [sup.3] , Saeed Saberi [sup.3] , Christoffer Hother [sup.1] , Anja Mottok [sup.1] [sup.4] , Fong Chun Chan [...]

Published
2020
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31. Pretransplant nivolumab further enhanced Treg expansion after posttransplant cyclophosphamide; another aspect for immune tolerance by PTCy after nivolumab

Author

Ikegawa, Shuntaro, Meguri, Yusuke, Mizuhara, Kentaro, Fukumi, Takuya, Kobayashi, Hiroki, Sumii, Yuichi, Kondo, Takumi, Sando, Yasuhisa, Iwamoto, Miki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Fujisawa, Yuka, Imai, Toshi, Maeda, Yoshinobu, and Matsuoka, Ken-ichi

Published
2021
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32. Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma

Author

Makino, Keigo, Otani, Yoshihiro, Fujii, Kentaro, Ishida, Joji, Hirano, Shuichiro, Suruga, Yasuki, Washio, Kana, Nishida, Kenji, Yanai, Hiroyuki, Tomida, Shuta, Ennishi, Daisuke, and Date, Isao

Subjects
genome-wide DNA methylation, comprehensive genomic profiling, pediatric brain tumor, MYCN
Abstract

In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.

Published
2023

33. Tumor-associated antigen PRAME exhibits dualistic functions that are targetable in diffuse large B cell lymphoma

Author

Takata, Katsuyoshi, Chong, Lauren C., Ennishi, Daisuke, Aoki, Tomohiro, Li, Michael Yu, Thakur, Avinash, Healy, Shannon, Vigano, Elena, Dao, Tao, Kwon, Daniel, Duns, Gerben, Nielsen, Julie S., Ben-Neriah, Susana, Tse, Ethan, Hung, Stacy S., Boyle, Merrill, Mun, Sung Soo, Bourne, Christopher M., Woolcock, Bruce, Telenius, Adele, Kishida, Makoto, Rai, Shinya, Zhang, Allen W., Bashashati, Ali, Saberi, Saeed, DAntonio, Gianluca, Nelson, Brad H., Shah, Sohrab P., Hoodless, Pamela A., Melnick, Ari M., Gascoyne, Randy D., Connors, Joseph M., Scheinberg, David A., Beguelin, Wendy, Scott, David W., and Steidl, Christian

Subjects
Oncology, Experimental, Gene mutations -- Research, Immune response -- Genetic aspects, Non-Hodgkin's lymphomas -- Genetic aspects -- Care and treatment, Tumor antigens -- Genetic aspects, Cancer -- Research, Health care industry
Abstract

PRAME is a prominent member of the cancer testis antigen family of proteins, which triggers autologous T cell-mediated immune responses. Integrative genomic analysis in diffuse large B cell lymphoma (DLBCL) uncovered recurrent and highly focal deletions of 22q11.22, including the PRAME gene, which were associated with poor outcome. PRAME-deleted tumors showed cytotoxic T cell immune escape and were associated with cold tumor microenvironments. In addition, PRAME downmodulation was strongly associated with somatic EZH2 Y641 mutations in DLBCL. In turn, PRC2-regulated genes were repressed in isogenic PRAME-KO lymphoma cell lines, and PRAME was found to directly interact with EZH2 as a negative regulator. EZH2 inhibition with EPZ-6438 abrogated these extrinsic and intrinsic effects, leading to PRAME expression and microenvironment restoration in vivo. Our data highlight multiple functions of PRAME during lymphomagenesis and provide a preclinical rationale for synergistic therapies combining epigenetic reprogramming with PRAME-targeted therapies., Introduction The current treatment standard of combined immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has achieved significant improvement in patient outcomes in diffuse large B cell lymphoma (DLBCL) [...]

Published
2022
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36. Genetic profiling of MYC and BCL2 in diffuse large B-cell lymphoma determines cell-of-origin–specific clinical impact

Author

Ennishi, Daisuke, Mottok, Anja, Ben-Neriah, Susana, Shulha, Hennady P., Farinha, Pedro, Chan, Fong Chun, Meissner, Barbara, Boyle, Merrill, Hother, Christoffer, Kridel, Robert, Lai, Daniel, Saberi, Saeed, Bashashati, Ali, Shah, Sohrab P., Morin, Ryan D., Marra, Marco A., Savage, Kerry J., Sehn, Laurie H., Steidl, Christian, Connors, Joseph M., Gascoyne, Randy D., and Scott, David W.

Published
2017
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37. Genomic Profiling of a Case of Glioneuronal Tumor with Neuropil-like Islands

Author

Tsuboi, Nobushige, Ishida, Joji, Shimazu, Yosuke, Edaki, Hisanori, Uneda, Atsuhito, Otani, Yoshihiro, Fujii, Kentaro, Kurozumi, Kazuhiko, Ennishi, Daisuke, Yanai, Hiroyuki, and Date, Isao

Subjects
glioneuronal tumor with neuropil-like islands, genomic profiling
Abstract

Glioneuronal tumor with neuropil-like islands (GNTNI) is a very rare subtype of glioneuronal tumor. We present a case of a 62-year-old man with GNTNI. Two adjacent lesions in the left parietal lobe were removed by left parietal craniotomy. The histological findings were glial cell proliferation and scattered rosettes consisting of synaptophysin-positive and NeuN-positive cells, leading to the diagnosis of GNTNI. Target sequencing revealed a genetic alteration similar to glioblastoma, IDH-wild type, which suggested adjuvant therapies. There are few previous reports on the treatment of this disease, and the patient should be followed carefully.

Published
2022

38. Evaluating the efficiency and safety of large‐volume leukapheresis using the Spectra Optia continuous mononuclear cell collection protocol for peripheral blood stem cell collection from healthy donors: A retrospective study.

Author

Sumii, Yuichi, Fujii, Keiko, Kondo, Takumi, Urata, Tomohiro, Kimura, Maiko, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Matsuoka, Ken‐ichi, Otsuka, Fumio, Maeda, Yoshinobu, and Fujii, Nobuharu

Subjects
STEM cells, BLOOD cells, STEM cell transplantation, BLOOD volume, BLOOD platelets, LEUKAPHERESIS, CD34 antigen
Abstract

Background: Large‐volume leukapheresis (LVL) refers to processing of more than three volumes of blood in a single session for peripheral blood stem cell collection. Recently, continuous mononuclear cell collection (cMNC) protocol has been developed using the Spectra Optia system, which is a widely used apheresis device. LVL using the novel protocol has been investigated in patients. However, the efficiency and safety of LVL in healthy donors using this protocol has not been characterized. Therefore, this study aimed to evaluate the efficiency and tolerability of CD34+ collection of LVL with the cMNC protocol in healthy donors. Study Design and Methods: We retrospectively collected data on LVL (>3 total blood volume) and normal‐volume leukapheresis (NVL) performed in healthy donors between October 2019 and December 2021. All procedures were performed using the cMNC protocol. Results: Although pre‐apheresis CD34+ cell count was lesser in LVL (23.5 vs. 58.0/μL, p <.001), CD34+ collection efficiency was comparable between LVL and NVL (61.2% vs. 61.4%, p =.966). Platelet loss was significantly higher in LVL compared to NVL (38.0% vs. 29.4%, p <.001), with no correlation between attrition of platelet and processing blood volume. Moreover, the incidence of citrate toxicity during procedures was comparable between the two groups (31.6% vs. 21.4%, p =.322). All LVL procedures could be completed without any adverse events. Conclusion: Allogeneic LVL procedure using Spectra Optia cMNC protocol was well tolerated by the donors and resulted in efficient collection of CD34+ cells, which was comparable to that of NVL. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch

Author

Kondo, Takumi, Fujii, Keiko, Fujii, Nobuharu, Sumii, Yuichi, Urata, Tomohiro, Kimura, Maiko, Matsuda, Masayuki, Ikegawa, Shuntaro, Washio, Kana, Fujiwara, Hideaki, Asada, Noboru, Ennishi, Daisuke, Nishimori, Hisakazu, Matsuoka, Ken‐ichi, Otsuka, Fumio, and Maeda, Yoshinobu

Subjects
blood center operations, therapeutic apheresis, cellular therapy
Abstract

Background: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES. Study Design and Methods: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods. Results: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation. Conclusion: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection.

Published
2023

42. Cell of origin of transformed follicular lymphoma

Author

Kridel, Robert, Mottok, Anja, Farinha, Pedro, Ben-Neriah, Susana, Ennishi, Daisuke, Zheng, Yvonne, Chavez, Elizabeth A., Shulha, Hennady P., Tan, King, Chan, Fong Chun, Boyle, Merrill, Meissner, Barbara, Telenius, Adele, Sehn, Laurie H., Marra, Marco A., Shah, Sohrab P., Steidl, Christian, Connors, Joseph M., Scott, David W., and Gascoyne, Randy D.

Published
2015
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44. Long non‐coding RNAs associated with transcriptomic signatures and treatment outcome in diffuse large B‐cell lymphoma.

Author

Duns, Gerben, Winkle, Melanie, Chong, Lauren, Ennishi, Daisuke, Morin, Ryan D., Diepstra, Arjan, Scott, David W., Kluiver, Joost L., Steidl, Christian, and van den Berg, Anke

Subjects
LINCRNA, GENE expression, DIFFUSE large B-cell lymphomas, TREATMENT effectiveness, TRANSCRIPTOMES
Abstract

Long non-coding RNAs associated with transcriptomic signatures and treatment outcome in diffuse large B-cell lymphoma I PVT1 i transcript levels might represent a promising marker for poor prognosis in this subset of DLBCL, but whether overexpression of I PVT1 i actively contributes to an aggressive clinical phenotype in these MYC-dysregulated tumours remains to be elucidated. I PVT1 i transcript levels are on average higher in I MYC i -translocated samples and DZsig-pos cases compared with other GCB-DLBCLs (Figure 2B), and do not show a significant correlation with I MYC i transcript levels in GCB-DLBCL, regardless of I MYC i translocation or DZsig status (Figure S9). To identify COO-specific associations we restricted the univariate COX regression analysis to ABC-DLBCL or GCB-DLBCL samples. [Extracted from the article]

Published
2023
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45. Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T‐cell therapy.

Author

Kitamura, Wataru, Asada, Noboru, Naoi, Yusuke, Abe, Masaya, Fujiwara, Hideaki, Ennishi, Daisuke, Nishimori, Hisakazu, Fujii, Keiko, Fujii, Nobuharu, Matsuoka, Ken‐ichi, Yoshino, Tadashi, and Maeda, Yoshinobu

Subjects
BONE marrow, DIFFUSE large B-cell lymphomas, T cells, STEM cell factor, CHIMERIC antigen receptors
Abstract

Summary: Mechanisms of prolonged cytopenia (PC) after chimeric antigen receptor (CAR) T‐cell therapy, an emerging therapy for relapsed or refractory diffuse large B‐cell lymphoma, remain elusive. Haematopoiesis is tightly regulated by the bone marrow (BM) microenvironment, called the 'niche'. To investigate whether alterations in the BM niche cells are associated with PC, we analysed CD271+ stromal cells in BM biopsy specimens and the cytokine profiles of the BM and serum obtained before and on day 28 after CAR T‐cell infusion. Imaging analyses of the BM biopsy specimens revealed that CD271+ niche cells were severely impaired after CAR T‐cell infusion in patients with PC. Cytokine analyses after CAR T‐cell infusion showed that CXC chemokine ligand 12 and stem cell factor, niche factors essential for haematopoietic recovery, were significantly decreased in the BM of patients with PC, suggesting reduced niche cell function. The levels of inflammation‐related cytokines on day 28 after CAR T‐cell infusion were consistently high in the BM of patients with PC. Thus, we demonstrate for the first time that BM niche disruption and sustained elevation of inflammation‐related cytokines in the BM following CAR T‐cell infusion are associated with subsequent PC. [ABSTRACT FROM AUTHOR]

Published
2023
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46. Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma

Author

Arthur, Sarah E., Jiang, Aixiang, Grande, Bruno M., Alcaide, Miguel, Cojocaru, Razvan, Rushton, Christopher K., Mottok, Anja, Hilton, Laura K., Lat, Prince Kumar, Zhao, Eric Y., Culibrk, Luka, Ennishi, Daisuke, Jessa, Selin, Chong, Lauren, Thomas, Nicole, Pararajalingam, Prasath, Meissner, Barbara, Boyle, Merrill, Davidson, Jordan, Bushell, Kevin R., Lai, Daniel, Farinha, Pedro, Slack, Graham W., Morin, Gregg B., Shah, Sohrab, Sen, Dipankar, Jones, Steven J. M., Mungall, Andrew J., Gascoyne, Randy D., Audas, Timothy E., Unrau, Peter, Marra, Marco A., Connors, Joseph M., Steidl, Christian, Scott, David W., and Morin, Ryan D.

Published
2018
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47. Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry

Author

Pastore, Alessandro, Jurinovic, Vindi, Kridel, Robert, Hoster, Eva, Staiger, Annette M, Szczepanowski, Monika, Pott, Christiane, Kopp, Nadja, Murakami, Mark, Horn, Heike, Leich, Ellen, Moccia, Alden A, Mottok, Anja, Sunkavalli, Ashwini, Van Hummelen, Paul, Ducar, Matthew, Ennishi, Daisuke, Shulha, Hennady P, Hother, Christoffer, Connors, Joseph M, Sehn, Laurie H, Dreyling, Martin, Neuberg, Donna, Möller, Peter, Feller, Alfred C, Hansmann, Martin L, Stein, Harald, Rosenwald, Andreas, Ott, German, Klapper, Wolfram, Unterhalt, Michael, Hiddemann, Wolfgang, Gascoyne, Randy D, Weinstock, David M, and Weigert, Oliver

Published
2015
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49. Clinical Impact of Cell-of-Origin and Double-Hit Signature of DLBCL in Japan

Author

Urata, Tomohiro, Sunami, Kazutaka, Imai, Toshi, Nawa, Yuichiro, Hiramatsu, Yasushi, Yamamoto, Kazuhiko, Fujii, Soichiro, Yoshida, Isao, Yano, Tomofumi, Naoi, Yusuke, Ikeuchi, Kazuhiro, Kobayashi, Hiroki, Tani, Katsuma, Momose, Shuji, Tamaru, Jun-ichi, Boyle, Merrill, Jiang, Aixiang, Sato, Yasuharu, Yoshino, Tadashi, Maeda, Yoshinobu, Scott, David W., and Ennishi, Daisuke

Published
2022
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50. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development

Author

Ortega-Molina, Ana, Boss, Isaac W., Canela, Andres, Pan, Heng, Jiang, Yanwen, Zhao, Chunying, Jiang, Man, Hu, Deqing, Agirre, Xabier, Niesvizky, Itamar, Lee, Ji-Eun, Chen, Hua-Tang, Ennishi, Daisuke, Scott, David W., Mottok, Anja, Hother, Christoffer, Liu, Shichong, Cao, Xing-Jun, Tam, Wayne, Shaknovich, Rita, Garcia, Benjamin A., Gascoyne, Randy D., Ge, Kai, Shilatifard, Ali, Elemento, Olivier, Nussenzweig, Andre, Melnick, Ari M., and Wendel, Hans-Guido

Subjects
Gene expression -- Analysis, Non-Hodgkin's lymphomas -- Genetic aspects -- Research -- Risk factors, Cancer -- Genetic aspects, Biological sciences, Health
Abstract

The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways., A majority of B cell lymphomas-including follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL), the most common forms of non-Hodgkin lymphoma-arise from germinal center (GC) B cells. GCs [...]

Published
2015
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