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6 results on '"Kensuke Usuki"'

1. Post-azacitidine clone size predicts outcome of patients with myelodysplastic syndromes and related myeloid neoplasms

Author

Yasuhito Nannya, Magnus Tobiasson, Shinya Sato, Elsa Bernard, Shigeki Ohtake, June Takeda, Maria Creignou, Lanying Zhao, Manabu Kusakabe, Yuhei Shibata, Nobuhiko Nakamura, Mizuki Watanabe, Nobuhiro Hiramoto, Yusuke Shiozawa, Yuichi Shiraishi, Hiroko Tanaka, Kenichi Yoshida, Nobuyuki Kakiuchi, Hideki Makishima, Masahiro Marshall Nakagawa, Kensuke Usuki, Mitsumasa Watanabe, Kazunori Imada, Hiroshi Handa, Masataka Taguchi, Toru Kiguchi, Kazuma Ohyashiki, Takayuki Ishikawa, Akifumi Takaori-Kondo, Hisashi Tsurumi, Senji Kasahara, Shigeru Chiba, Tomoki Naoe, Satoru Miyano, Elli Papaemmanuil, Yasushi Miyazaki, Eva Hellström Lindberg, and Seishi Ogawa

Subjects
Hematology
Abstract

Azacitidine is a mainstay of therapy for MDS-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their post-treatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms. They were analyzed for gene mutations in pre- (n=449) and post- (n=289) treatment bone marrow samples using targeted-capture sequencing to assess the impact of gene mutations and their post-treatment clone size on treatment outcomes. In Cox proportional hazard modeling, multi-hit TP53 mutation (HR, 2.03; 95% CI, 1.42-2.91; P

Published
2023

2. Prognostic impact of CEBPA bZIP domain mutation in acute myeloid leukemia

Author

Ayumi Mizoguchi, Atsushi Marumo, Nobuhiko Uoshima, Eriko Sato, Satoshi Wakita, Hiroki Yamaguchi, Eri Kawata, Kenji Tajika, Jiro Tadokoro, Yuhei Nagao, Tomoaki Kitano, Iekuni Oh, Kunihito Arai, Yasushi Kubota, Shinichi Kako, Ikuko Omori, Hisao Nagoshi, Shinichiro Mori, Koiti Inokuchi, Yoshinobu Kanda, Sayuri Motomura, Naoyuki Uchida, Yutaka Kobayashi, Hideharu Muto, Junya Kuroda, Toshimitsu Ueki, Miho Miyata, Noriko Doki, Saiko Kurosawa, Masao Ogata, Takahiro Fukuda, Norio Komatsu, Kenjiro Mitsuhashi, Takashi Toya, Jun Ando, Shinya Kimura, Katsuhiro Shono, Hitoji Uchiyama, Kazuki Terada, Masao Hagihara, Kensuke Kayamori, Atsushi Satake, Kazuteru Ohashi, Kensuke Usuki, Akiko Hashimoto, Akiyo Kurosawa, Junya Kanda, Shunsuke Yui, Motoharu Shibusawa, Yusuke Fujiwara, Yuho Najima, Tatsuo Ichinohe, and Masahiro Sakaguchi

Subjects
Oncology, medicine.medical_specialty, animal structures, genetic processes, Karyotype, information science, medicine.disease_cause, Lower risk, environment and public health, Internal medicine, Enhancer binding, hemic and lymphatic diseases, CEBPA, medicine, CCAAT-Enhancer-Binding Protein-alpha, Humans, Cumulative incidence, Aged, Mutation, Myeloid Neoplasia, business.industry, Hazard ratio, Myeloid leukemia, bZIP domain, Hematology, Prognosis, Leukemia, Myeloid, Acute, CCAAT-Enhancer-Binding Proteins, business
Abstract

Key Points CEBPA mutation in the bZIP domain is associated with favorable prognosis in de novo AML, even if it was detected as CEBPAsm., Visual Abstract, Mutations of CCAAT/enhancer–binding protein alpha (CEBPAmu) are found in 10% to 15% of de novo acute myeloid leukemia (AML) cases. Double-mutated CEBPA (CEBPAdm) is associated with a favorable prognosis; however, single-mutated CEBPA (CEBPAsm) does not seem to improve prognosis. We investigated CEBPAmu for prognosis in 1028 patients with AML, registered in the Multi-center Collaborative Program for Gene Sequencing of Japanese AML. It was found that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. The presence of CEBPAmu in bZIP was a strong indicator of a higher chance of achieving complete remission (P < .001), better overall survival (OS; P < .001) and a lower risk of relapse (P < .001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm (all patients: OS, P = .008; the cumulative incidence of relapse, P = .063; patients aged ≤70 years and with intermediate-risk karyotype: OS, P = .008; cumulative incidence of relapse, P = .026). Multivariate analysis of 744 patients aged ≤70 years showed that CEBPAmu in bZIP was the most potent predictor of OS (hazard ratio, 0.3287; P < .001). CEBPAdm was validated as a cofounding factor, which was overlapping with CEBPAmu in bZIP. In summary, these findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis. It holds potential in the refinement of treatment stratification and the development of targeted therapeutic approaches in CEBPA-mutated AML.

Published
2021

3. Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia

Author

Ken Ishiyama, Saho Takasaki, Akio Tawa, Kenichi Chiba, Kazutaka Fukumura, Nobuhiro Hiramoto, Shuichi Miyawaki, Yasuhide Hayashi, Yasuhiko Kamikubo, Yasushi Miyazaki, Kenichi Yoshida, Hiroki Yamaguchi, Yuki Noguchi, Hiroko Tanaka, Machiko Kawamura, Hidehiro Itonaga, Kensuke Usuki, Hiroshi Handa, Souichi Adachi, Yusuke Shiozawa, Hiroyuki Mano, Takayuki Ishikawa, Satoru Miyano, Yuichi Shiraishi, Genki Yamato, Hiroo Ueno, Kana Nakatani, Mina Noura, Seishi Ogawa, June Takeda, Yasuhito Nannya, Hidemasa Matsuo, Norio Shiba, Yuichiro Ono, Ai Okada, Takashi Taga, Nobutaka Kiyokawa, and Daisuke Tomizawa

Subjects
0301 basic medicine, Mutation, Myeloid, biology, Cohesin complex, business.industry, Myeloid leukemia, Hematology, Gene rearrangement, medicine.disease, medicine.disease_cause, Lymphoma, 03 medical and health sciences, Leukemia, 030104 developmental biology, KMT2A, medicine.anatomical_structure, hemic and lymphatic diseases, biology.protein, Cancer research, Medicine, business, neoplasms
Abstract

In acute myeloid leukemia (AML), MLL (KMT2A) rearrangements are among the most frequent chromosomal abnormalities; however, knowledge of the genetic landscape of MLL-rearranged AML is limited. In this study, we performed whole-exome sequencing (n = 9) and targeted sequencing (n = 56) of samples from pediatric MLL-rearranged AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. Additionally, we analyzed 105 pediatric t(8;21) AML samples and 30 adult MLL-rearranged AML samples. RNA-sequencing data from 31 patients published in a previous study were also reanalyzed. As a result, we identified 115 mutations in pediatric MLL-rearranged AML patients (2.1 mutations/patient), with mutations in signaling pathway genes being the most frequently detected (60.7%). Mutations in genes associated with epigenetic regulation (21.4%), transcription factors (16.1%), and the cohesin complex (8.9%) were also commonly detected. Novel CCND3 mutations were identified in 5 pediatric MLL-rearranged AML patients (8.9%) and 2 adult MLL-rearranged AML patients (3.3%). Recurrent mutations of CCND1 (n = 3, 2.9%) and CCND2 (n = 8, 7.6%) were found in pediatric t(8;21) AML patients, whereas no CCND3 mutations were found, suggesting that D-type cyclins exhibit a subtype-specific mutation pattern in AML. Treatment of MLL-rearranged AML cell lines with CDK4/6 inhibitors (abemaciclib and palbociclib) blocked G1 to S phase cell-cycle progression and impaired proliferation. Pediatric MLL-MLLT3–rearranged AML patients with coexisting mutations (n = 16) had significantly reduced relapse-free survival and overall survival compared with those without coexisting mutations (n = 9) (P = .048 and .046, respectively). These data provide insights into the genetics of MLL-rearranged AML and suggest therapeutic strategies., 急性骨髄性白血病の新規遺伝子変異を発見 --乳がんの既存薬が治療に有効である可能性--. 京都大学プレスリリース. 2018-11-01.

Published
2018

4. Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia

Author

Kunihito Arai, Saiko Kurosawa, Yoshinobu Kanda, Yuho Najima, Yasushi Kubota, Kenji Tajika, Atsushi Marumo, Toshimitsu Ueki, Iekuni Oh, Yusuke Fujiwara, Masahiro Sakaguchi, Shinichi Kako, Kazuhiko Kakihana, Hitoji Uchiyama, Junya Kanda, Kensuke Usuki, Shunsuke Yui, Katsuhiro Shono, Masao Hagihara, Kazuteru Ohashi, Takahiro Fukuda, Satoshi Wakita, Hiroki Yamaguchi, Kensuke Kayamori, S Mori, Yutaka Kobayashi, Tomoaki Kitano, Naoyuki Uchida, Ikuko Omori, Shinya Kimura, Eri Kawata, Nobuhiko Uoshima, Koiti Inokuchi, Seiji Gomi, Junya Kuroda, and Nana Nakajima

Subjects
0301 basic medicine, Oncology, NPM1, medicine.medical_specialty, Myeloid, business.industry, medicine.medical_treatment, Myeloid leukemia, Hematology, Hematopoietic stem cell transplantation, Gene mutation, medicine.disease, 03 medical and health sciences, European LeukemiaNet, Leukemia, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Internal medicine, medicine, Allele, business, psychological phenomena and processes
Abstract

In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)–positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (FLT3-ITD) allele ratio (AR)

Published
2018

5. Prognostic impact of low allelic ratio

Author

Masahiro, Sakaguchi, Hiroki, Yamaguchi, Yuho, Najima, Kensuke, Usuki, Toshimitsu, Ueki, Iekuni, Oh, Sinichiro, Mori, Eri, Kawata, Nobuhiko, Uoshima, Yutaka, Kobayashi, Shinichi, Kako, Kenji, Tajika, Seiji, Gomi, Katsuhiro, Shono, Kensuke, Kayamori, Masao, Hagihara, Junya, Kanda, Hitoji, Uchiyama, Junya, Kuroda, Naoyuki, Uchida, Yasushi, Kubota, Shinya, Kimura, Saiko, Kurosawa, Nana, Nakajima, Atsushi, Marumo, Ikuko, Omori, Yusuke, Fujiwara, Shunsuke, Yui, Satoshi, Wakita, Kunihito, Arai, Tomoaki, Kitano, Kazuhiko, Kakihana, Yoshinobu, Kanda, Kazuteru, Ohashi, Takahiro, Fukuda, and Koiti, Inokuchi

Subjects
Adult, Aged, 80 and over, Male, Myeloid Neoplasia, Adolescent, Nuclear Proteins, hemic and immune systems, Middle Aged, Prognosis, body regions, Leukemia, Myeloid, Acute, Young Adult, fms-Like Tyrosine Kinase 3, hemic and lymphatic diseases, embryonic structures, Mutation, Humans, Female, Nucleophosmin, psychological phenomena and processes, Aged, Retrospective Studies
Abstract

The ELN guideline classifying FLT3-ITD low allele ratio with NPM1 mutation as having a favorable prognosis is questionable.Performing allo-HSCT during CR1 irrespective of the FLT3-ITD allele ratio and NPM1 mut status significantly improves outcome.

Published
2018

6. Recurrent

Author

Hidemasa, Matsuo, Kenichi, Yoshida, Kazutaka, Fukumura, Kana, Nakatani, Yuki, Noguchi, Saho, Takasaki, Mina, Noura, Yusuke, Shiozawa, Yuichi, Shiraishi, Kenichi, Chiba, Hiroko, Tanaka, Ai, Okada, Yasuhito, Nannya, June, Takeda, Hiroo, Ueno, Norio, Shiba, Genki, Yamato, Hiroshi, Handa, Yuichiro, Ono, Nobuhiro, Hiramoto, Takayuki, Ishikawa, Kensuke, Usuki, Ken, Ishiyama, Shuichi, Miyawaki, Hidehiro, Itonaga, Yasushi, Miyazaki, Machiko, Kawamura, Hiroki, Yamaguchi, Nobutaka, Kiyokawa, Daisuke, Tomizawa, Takashi, Taga, Akio, Tawa, Yasuhide, Hayashi, Hiroyuki, Mano, Satoru, Miyano, Yasuhiko, Kamikubo, Seishi, Ogawa, and Souichi, Adachi

Subjects
Gene Rearrangement, Male, Myeloid Neoplasia, Adolescent, DNA Copy Number Variations, Infant, Newborn, Infant, Histone-Lysine N-Methyltransferase, G1 Phase Cell Cycle Checkpoints, Survival Rate, Leukemia, Myeloid, Acute, Recurrence, hemic and lymphatic diseases, Child, Preschool, Cyclin D, Mutation, Humans, Female, RNA Interference, Cyclin D3, RNA, Small Interfering, Child, neoplasms, Protein Kinase Inhibitors, Myeloid-Lymphoid Leukemia Protein
Abstract

Novel CCND3 mutations were identified, and CDK4/6 inhibitors represent a promising therapeutic option for MLL-rearranged AML.Coexisting mutations had a negative prognostic impact on pediatric MLL-MLLT3–rearranged AML patients.

Published
2018

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