Updated on 2024/10/07

Information

 

写真a

 
HIRABAYASHI SHIGEKI
 
Organization
Faculty of Medical Sciences Department of Clinical Medicine Assistant Professor
Faculty of Medical Sciences Research Center for Precision Medicine(Concurrent)
School of Medicine Department of Medicine(Concurrent)
Title
Assistant Professor
External link

Research Areas

  • Life Science / Hematology and medical oncology

  • Life Science / System genome science

Degree

  • Bachelor (Pharmacy) (Nagoya City University)

  • Bachelor (Medicine) (Niigata University)

  • Doctor (Medicine) (Kyoto University)

Research History

  • Kyushu University Faculty of Medical Sciences Assistant Professor 

    2022.3 - Present

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  • Kyushu University Faculty of Medical Sciences 特任助教/学術研究員 

    2021.4 - 2022.2

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Research Interests・Research Keywords

  • Research theme: Searching for new cancer treatment targets based on large-scale genomics and functional screening

    Keyword: CRISPR screening

    Research period: 2022.4 - 2022.6

Awards

  • ふくおか「臨床医学研究賞」

    2022.3  

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    DDX41変異を有する骨髄系腫瘍の遺伝子発現制御機構の解明とその治療法の開発を行う

  • ふくおか「臨床医学研究賞」

    2022  

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  • 日本臨床腫瘍学会奨励賞

    2021.2  

  • 日本血液学会奨励賞

    2020.10  

  • 有壬記念学術奨励賞

    2020.6  

  • 理研梅峰賞

    2020.3  

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Papers

  • Impact of MRD on clinical outcomes of unrelated hematopoietic stem cell transplantation in patients with Ph+ALL: A retrospective nationwide study Reviewed

    Shigeki Hirabayashi, Tadakazu Kondo, Satoshi Nishiwaki, Shuichi Mizuta, Noriko Doki, Takahiro Fukuda, Naoyuki Uchida, Yukiyasu Ozawa, Yoshinobu Kanda, Ryota Imanaka, Satoshi Takahashi, Jun Ishikawa, Shingo Yano, Hirohisa Nakamae, Tetsuya Eto, Takafumi Kimura, Junji Tanaka, Tatsuo Ichinohe, Yoshiko Atsuta, Shinichi Kako

    American Journal of Hematology   2023.7

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    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ajh.27041

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  • Personalized prediction of overall survival in patients with AML in non‐complete remission undergoing allo‐HCT Reviewed

    Shigeki Hirabayashi, Ryuji Uozumi, Tadakazu Kondo, Yasuyuki Arai, Takahito Kawata, Naoyuki Uchida, Atsushi Marumo, Kazuhiro Ikegame, Takahiro Fukuda, Tetsuya Eto, Masatsugu Tanaka, Atsushi Wake, Junya Kanda, Takafumi Kimura, Ken Tabuchi, Tatsuo Ichinohe, Yoshiko Atsuta, Masamitsu Yanada, Shingo Yano

    Cancer Medicine   2021.6

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    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/cam4.3920

  • APOBEC3B is preferentially expressed at the G2/M phase of cell cycle Reviewed

    Shigeki Hirabayashi, Kotaro Shirakawa, Yoshihito Horisawa, Tadahiko Matsumoto, Hiroyuki Matsui, Hiroyuki Yamazaki, Anamaria Daniela Sarca, Yasuhiro Kazuma, Ryosuke Nomura, Yoshinobu Konishi, Suguru Takeuchi, Emani Stanford, Hideya Kawaji, Yasuhiro Murakawa, Akifumi Takaori-Kondo

    Biochemical and Biophysical Research Communications   546   178 - 184   2021.3

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    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2021.02.008

  • NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements Reviewed International journal

    Shigeki Hirabayashi, Shruti Bhagat, Yu Matsuki, Yujiro Takegami, Takuya Uehata, Ai Kanemaru, Masayoshi Itoh, Kotaro Shirakawa, Akifumi Takaori-Kondo, Osamu Takeuchi, Piero Carninci, Shintaro Katayama, Yoshihide Hayashizaki, Juha Kere, Hideya Kawaji, Yasuhiro Murakawa

    Nature Genetics   51 ( 9 )   1369 - 1379   2019.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    Promoters and enhancers are key cis-regulatory elements, but how they operate to generate cell type-specific transcriptomes is not fully understood. We developed a simple and robust method, native elongating transcript-cap analysis of gene expression (NET-CAGE), to sensitively detect 5' ends of nascent RNAs in diverse cells and tissues, including unstable transcripts such as enhancer-derived RNAs. We studied RNA synthesis and degradation at the transcription start site level, characterizing the impact of differential promoter usage on transcript stability. We quantified transcription from cis-regulatory elements without the influence of RNA turnover, and show that enhancer-promoter pairs are generally activated simultaneously on stimulation. By integrating NET-CAGE data with chromatin interaction maps, we show that cis-regulatory elements are topologically connected according to their cell type specificity. We identified new enhancers with high sensitivity, and delineated primary locations of transcription within super-enhancers. Our NET-CAGE dataset derived from human and mouse cells expands the FANTOM5 atlas of transcribed enhancers, with broad applicability to biomedical research.

    DOI: 10.1038/s41588-019-0485-9

  • Successful treatment of severe acute gastrointestinal graft-versus-host disease complicated by cytomegalovirus gastroenteritis with intra-arterial steroid infusion. Reviewed

    Hirabayashi S, Kondo T, Oka T, Akamatsu Y, Hishizawa M, Shibata T, Kitano T, Takaori-Kondo A

    Annals of hematology   2016.8

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    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00277-016-2686-y

  • Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer. Reviewed International journal

    Hirabayashi S, Kosugi S, Isobe Y, Nashimoto A, Oda I, Hayashi K, Miyashiro I, Tsujitani S, Kodera Y, Seto Y, Furukawa H, Ono H, Tanabe S, Akazawa K

    Annals of oncology : official journal of the European Society for Medical Oncology   25 ( 6 )   1179 - 84   2014.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

    DOI: 10.1093/annonc/mdu125

  • The RNA helicases DDX19A/B modulate selinexor sensitivity by regulating <i>MCL1</i> mRNA nuclear export in leukemia cells

    Terasaki, T; Semba, Y; Sasaki, K; Imanaga, H; Setoguchi, K; Yamauchi, T; Hirabayashi, S; Nakao, F; Akahane, K; Inukai, T; Sanda, T; Akashi, K; Maeda, T

    LEUKEMIA   38 ( 9 )   1918 - 1928   2024.7   ISSN:0887-6924 eISSN:1476-5551

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    Language:English   Publisher:Leukemia  

    Selinexor, a first-in-class exportin1 (XPO1) inhibitor, is an attractive anti-tumor agent because of its unique mechanisms of action; however, its dose-dependent toxicity and lack of biomarkers preclude its wide use in clinical applications. To identify key molecules/pathways regulating selinexor sensitivity, we performed genome-wide CRISPR/Cas9 dropout screens using two B-ALL lines. We identified, for the first time, that paralogous DDX19A and DDX19B RNA helicases modulate selinexor sensitivity by regulating MCL1 mRNA nuclear export. While single depletion of either DDX19A or DDX19B barely altered MCL1 protein levels, depletion of both significantly attenuated MCL1 mRNA nuclear export, reducing MCL1 protein levels. Importantly, combining selinexor treatment with depletion of either DDX19A or DDX19B markedly induced intrinsic apoptosis of leukemia cells, an effect rescued by MCL1 overexpression. Analysis of Depmap datasets indicated that a subset of T-ALL lines expresses minimal DDX19B mRNA levels. Moreover, we found that either selinexor treatment or DDX19A depletion effectively induced apoptosis of T-ALL lines expressing low DDX19B levels. We conclude that XPO1 and DDX19A/B coordinately regulate cellular MCL1 levels and propose that DDX19A/B could serve as biomarkers for selinexor treatment. Moreover, pharmacological targeting of DDX19 paralogs may represent a potential strategy to induce intrinsic apoptosis in leukemia cells.

    DOI: 10.1038/s41375-024-02343-2

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  • An atlas of transcribed enhancers across helper T cell diversity for decoding human diseases.

    Oguchi A, Suzuki A, Komatsu S, Yoshitomi H, Bhagat S, Son R, Bonnal RJP, Kojima S, Koido M, Takeuchi K, Myouzen K, Inoue G, Hirai T, Sano H, ITEC Consortium Members

    Science (New York, N.Y.)   385 ( 6704 )   eadd8394   2024.7   ISSN:0036-8075

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Science (New York, N.Y.)  

    Transcribed enhancer maps can reveal nuclear interactions underpinning each cell type and connect specific cell types to diseases. Using a 5' single-cell RNA sequencing approach, we defined transcription start sites of enhancer RNAs and other classes of coding and noncoding RNAs in human CD4+ T cells, revealing cellular heterogeneity and differentiation trajectories. Integration of these datasets with single-cell chromatin profiles showed that active enhancers with bidirectional RNA transcription are highly cell type-specific and that disease heritability is strongly enriched in these enhancers. The resulting cell type-resolved multimodal atlas of bidirectionally transcribed enhancers, which we linked with promoters using fine-scale chromatin contact maps, enabled us to systematically interpret genetic variants associated with a range of immune-mediated diseases.

    DOI: 10.1126/science.add8394

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  • Genome-Wide CRISPR/Cas9 Screens Identify DDX19A/DDX19B As a Critical Regulator of Intrinsic Apoptosis By Regulating MCL1 mRNA Cellular Localization

    Terasaki, T; Semba, Y; Sasaki, K; Miyata, K; Yamauchi, T; Imanaga, H; Nakao, F; Hirabayashi, S; Nogami, J; Akahane, K; Inukai, T; Akashi, K; Maeda, T

    BLOOD   142   2023.11   ISSN:0006-4971 eISSN:1528-0020

  • Identification of Novel Transcripts and Potential Therapeutic Targets for Acute Leukemia

    Wada, F; Kato, S; Bhagat, S; Hirabayashi, S; Son, R; Oguchi, A; Takeuchi, K; Sekito, S; Hirai, T; Zhang, ZW; Horisawa, Y; Iwasaki, M; Takeda, J; Kanda, J; Sakamoto, T; Shirakawa, K; Takaori-Kondo, A; Murakawa, Y

    BLOOD   142   2023.11   ISSN:0006-4971 eISSN:1528-0020

  • Targeting a mitochondrial E3 ubiquitin ligase complex to overcome AML cell-intrinsic Venetoclax resistance. Reviewed International journal

    Nakao F, Setoguchi K, Semba Y, Yamauchi T, Nogami J, Sasaki K, Imanaga H, Terasaki T, Miyazaki M, Hirabayashi S, Miyawaki K, Kikushige Y, Masuda T, Akashi K, Maeda T.

    Leukemia   2023.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41375-023-01879-z

  • Targeting a mitochondrial E3 ubiquitin ligase complex to overcome AML cell-intrinsic Venetoclax resistance. International journal

    Fumihiko Nakao, Kiyoko Setoguchi, Yuichiro Semba, Takuji Yamauchi, Jumpei Nogami, Kensuke Sasaki, Hiroshi Imanaga, Tatsuya Terasaki, Manaka Miyazaki, Shigeki Hirabayashi, Kohta Miyawaki, Yoshikane Kikushige, Takeshi Masuda, Koichi Akashi, Takahiro Maeda

    Leukemia   2023.3

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    To identify molecules/pathways governing Venetoclax (VEN) sensitivity, we performed genome-wide CRISPR/Cas9 screens using a mouse AML line insensitive to VEN-induced mitochondrial apoptosis. Levels of sgRNAs targeting March5, Ube2j2 or Ube2k significantly decreased upon VEN treatment, suggesting synthetic lethal interaction. Depletion of either Ube2j2 or Ube2k sensitized AML cells to VEN only in the presence of March5, suggesting coordinate function of the E2s Ube2j2 and Ube2k with the E3 ligase March5. We next performed CRISPR screens using March5 knockout cells and identified Noxa as a key March5 substrate. Mechanistically, Bax released from Bcl2 upon VEN treatment was entrapped by Mcl1 and Bcl-XL and failed to induce apoptosis in March5 intact AML cells. By contrast, in March5 knockout cells, liberated Bax did not bind to Mcl1, as Noxa likely occupied Mcl1 BH3-binding grooves and efficiently induced mitochondrial apoptosis. We reveal molecular mechanisms underlying AML cell-intrinsic VEN resistance and suggest a novel means to sensitize AML cells to VEN.

    DOI: 10.1038/s41375-023-01879-z

  • HTLV-1 bZIP factor impairs DNA mismatch repair system. International journal

    Maki Sakurada-Aono, Takashi Sakamoto, Masayuki Kobayashi, Yoko Takiuchi, Fumie Iwai, Kohei Tada, Hiroyuki Sasanuma, Shigeki Hirabayashi, Yasuhiro Murakawa, Kotaro Shirakawa, Chihiro Sakamoto, Keisuke Shindo, Jun-Ichirou Yasunaga, Masao Matsuoka, Yves Pommier, Shunichi Takeda, Akifumi Takaori-Kondo

    Biochemical and biophysical research communications   657   43 - 49   2023.3

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    Adult T-cell leukemia (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). Microsatellite instability (MSI) has been observed in ATL cells. Although MSI results from impaired mismatch repair (MMR) pathway, no null mutations in the genes encoding MMR factors are detectable in ATL cells. Thus, it is unclear whether or not impairment of MMR causes the MSI in ATL cells. HTLV-1 bZIP factor (HBZ) protein interacts with numerous host transcription factors and significantly contributes to disease pathogenesis and progression. Here we investigated the effect of HBZ on MMR in normal cells. The ectopic expression of HBZ in MMR-proficient cells induced MSI, and also suppressed the expression of several MMR factors. We then hypothesized that the HBZ compromises MMR by interfering with a transcription factor, nuclear respiratory factor 1 (NRF-1), and identified the consensus NRF-1 binding site at the promoter of the gene encoding MutS homologue 2 (MSH2), an essential MMR factor. The luciferase reporter assay revealed that NRF-1 overexpression enhanced MSH2 promoter activity, while co-expression of HBZ reversed this enhancement. These results supported the idea that HBZ suppresses the transcription of MSH2 by inhibiting NRF-1. Our data demonstrate that HBZ causes impaired MMR, and may imply a novel oncogenesis driven by HTLV-1.

    DOI: 10.1016/j.bbrc.2023.03.049

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  • A genome-wide CRISPR-Cas9 screen reveals GATOR1 complex as a critical regulator of glucocorticoid sensitivity in B-ALL

    Imanaga, H; Hirabayashi, S; Akashi, K; Maeda, T

    CANCER SCIENCE   114   440 - 440   2023.2   ISSN:1347-9032 eISSN:1349-7006

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  • A Genome-Wide CRISPR-Cas9 Screen Reveals GATOR1 Complex Is a Critical Regulator of Glucocorticoid Sensitivity in B-Cell Precursor Acute Lymphoblastic Leukemia

    Imanaga, H; Semba, Y; Sasaki, K; Miyata, K; Yamauchi, T; Terasaki, T; Nakao, F; Hirabayashi, S; Nogami, J; Akashi, K; Maeda, T

    BLOOD   140   5979 - 5979   2022.11   ISSN:0006-4971 eISSN:1528-0020

  • Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients.

    Jo T, Arai Y, Kondo T, Mizuno S, Hirabayashi S, Inamoto Y, Doki N, Fukuda T, Ozawa Y, Katayama Y, Kanda Y, Fukushima K, Matsuoka KI, Takada S, Yanada M

    Cytotherapy   24 ( 10 )   1013 - 1025   2022.6   ISSN:1465-3249 eISSN:1477-2566

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    Language:Others   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.jcyt.2022.05.009

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  • Effect of Multiple HLA Locus Mismatches on Outcomes after Single Cord Blood Transplantation. International journal

    Kanda J, Hirabayashi S, Yokoyama H, Kawase T, Tanaka H, Uchida N, Taniguchi S, Takahashi S, Onizuka M, Tanaka M, Sugio Y, Eto T, Kanda Y, Kimura T, Japanese Society for Transplantation and Cellular Therapy's HLA Working Group

    Transplantation and cellular therapy   28 ( 7 )   398.e1-398.e9   2022.5

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    The effect of single or multiple mismatches at each HLA locus on outcomes after cord blood transplantation (CBT) is controversial. We analyzed the effects of single or multiple HLA locus mismatches on the outcomes after single CBT using Japanese registry data from the Japan Society for Hematopoietic Cell Transplantation. Patients age ≥16 years with acute leukemia and myelodysplastic syndromes who underwent their first CBT between 2003 and 2017 (n = 4074) were included. The effect of the number of HLA locus mismatches (0, 1, or 2 for the HLA-A, -B, -C, and -DRB1 loci) on outcomes was analyzed after adjusting for other significant variables. The patient cohort had a median age of 54 years. The median total nucleated and CD34 cell doses were 2.6 × 107/kg and .8 × 105/kg, respectively. The number of CBTs with single or double mismatches were 2099 and 292, respectively, for the HLA-A locus, 2699 and 341 for the HLA-B locus, 2555 and 609 for the HLA-C locus, and 2593 and 571 for the HLA-DRB1 locus. Single and double HLA-DRB1 mismatches were associated with a higher risk of grade II-IV acute graft-versus-host disease (GVHD; single: hazard ratio [HR], 1.29, P < .001; double: HR, 1.49, P < .001; P for trend <.001). Single and double mismatches at HLA-DRB1 as well as single mismatches at HLA-A and HLA-B also were associated with grade III-IV acute GVHD. Single and double HLA-B mismatches and double HLA-DRB1 mismatches were associated with a high risk of nonrelapse mortality (NRM). On the other hand, double mismatches at HLA-A or HLA-DRB1 and single mismatches at HLA-B were associated with a lower risk of relapse. HLA-DRB1 double mismatch was associated with high risk of grade II-IV and grade III-IV acute GVHD and NRM but lower risk of relapse. Not only the locus mismatch, but also the number of mismatches, should be considered in cord blood unit selection.

    DOI: 10.1016/j.jtct.2022.05.005

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  • Comparing cord blood transplantation and matched related donor transplantation in non-remission acute myeloid leukemia Reviewed International journal

    Shimomura, Yoshimitsu; Sobue, Tomotaka; Hirabayashi, Shigeki; Kondo, Tadakazu; Mizuno, Shohei; Kanda, Junya; Fujino, Takahiro; Kataoka, Keisuke; Uchida, Naoyuki; Eto, Tetsuya; Miyakoshi, Shigesaburo; Tanaka, Masatsugu; Kawakita, Toshiro; Yokoyama, Hisayuki; Doki, Noriko; Harada, Kaito; Wake, Atsushi; Ota, Shuichi; Takada, Satoru; Takahashi, Satoshi; Kimura, Takafumi; Onizuka, Makoto; Fukuda, Takahiro; Atsuta, Yoshiko; Yanada, Masamitsu

    LEUKEMIA   36 ( 4 )   1132 - 1138   2021.11

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    Cord blood transplantation (CBT) is an alternative donor transplantation method and has the advantages of rapid availability and the possibility of inducing a more potent graft-versus-leukemia effect, leading to a lower relapse rate for patients with non-remission relapse and refractory acute myeloid leukemia (R/R AML). This study aimed to investigate the impact of CBT, compared to human leukocyte antigen-matched related donor transplantation (MRDT). This study included 2451 adult patients with non-remission R/R AML who received CBT (1738 patients) or MRDT (713 patients) between January 2009 and December 2018. Five-year progression-free survival (PFS) and the prognostic impact of CBT were evaluated using a propensity score (PS) matching analysis. After PS matching, the patient characteristics were well balanced between the groups. The five-year PFS was 25.2% (95% confidence interval [CI]: 21.2–29.5%) in the CBT group and 18.1% (95% CI: 14.5–22.0%) in the MRDT group (P = 0.009). The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.69–1.00, P = 0.045); this was due to a more pronounced decrease in the relapse rate (HR: 0.78, 95% CI: 0.69–0.89, P < 0.001) than an increase in the NRM (1.42, 1.15–1.76, P = 0.001). In this population, CBT was associated with a better 5-year PFS than MRDT after allogeneic HSCT.

    DOI: 10.1038/s41375-021-01474-0

  • Comparing cord blood transplantation and matched related donor transplantation in non-remission acute myeloid leukemia Reviewed

    Yoshimitsu Shimomura, Tomotaka Sobue, Shigeki Hirabayashi, Tadakazu Kondo, Shohei Mizuno, Junya Kanda, Takahiro Fujino, Keisuke Kataoka, Naoyuki Uchida, Tetsuya Eto, Shigesaburo Miyakoshi, Masatsugu Tanaka, Toshiro Kawakita, Hisayuki Yokoyama, Noriko Doki, Kaito Harada, Atsushi Wake, Shuichi Ota, Satoru Takada, Satoshi Takahashi, Takafumi Kimura, Makoto Onizuka, Takahiro Fukuda, Yoshiko Atsuta, Masamitsu Yanada

    Leukemia   36 ( 4 )   1132 - 1138   2021.11

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    Cord blood transplantation (CBT) is an alternative donor transplantation method and has the advantages of rapid availability and the possibility of inducing a more potent graft-versus-leukemia effect, leading to a lower relapse rate for patients with non-remission relapse and refractory acute myeloid leukemia (R/R AML). This study aimed to investigate the impact of CBT, compared to human leukocyte antigen-matched related donor transplantation (MRDT). This study included 2451 adult patients with non-remission R/R AML who received CBT (1738 patients) or MRDT (713 patients) between January 2009 and December 2018. Five-year progression-free survival (PFS) and the prognostic impact of CBT were evaluated using a propensity score (PS) matching analysis. After PS matching, the patient characteristics were well balanced between the groups. The five-year PFS was 25.2&#37; (95&#37; confidence interval [CI]: 21.2–29.5&#37;) in the CBT group and 18.1&#37; (95&#37; CI: 14.5–22.0&#37;) in the MRDT group (P = 0.009). The adjusted hazard ratio (HR) was 0.83 (95&#37; CI: 0.69–1.00, P = 0.045); this was due to a more pronounced decrease in the relapse rate (HR: 0.78, 95&#37; CI: 0.69–0.89, P < 0.001) than an increase in the NRM (1.42, 1.15–1.76, P = 0.001). In this population, CBT was associated with a better 5-year PFS than MRDT after allogeneic HSCT.

    DOI: 10.1038/s41375-021-01474-0

  • The differential effect of disease status at allogeneic hematopoietic cell transplantation on outcomes in acute myeloid and lymphoblastic leukemia. Reviewed International journal

    Yanada M, Konuma T, Yamasaki S, Mizuno S, Hirabayashi S, Nishiwaki S, Uchida N, Doki N, Tanaka M, Ozawa Y, Sawa M, Eto T, Kawakita T, Ota S, Yano S

    Annals of hematology   100 ( 12 )   3017 - 3027   2021.9

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    This study aimed to compare the effect of disease status at the time of allogeneic hematopoietic cell transplantation (HCT) on post-transplant outcomes between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Japanese nationwide registry data for 6901 patients with AML and 2469 patients with ALL were analyzed. In this study, 2850 (41&#37;), 937 (14&#37;), 62 (1&#37;), and 3052 (44&#37;) AML patients and 1751 (71&#37;), 265 (11&#37;), 23 (1&#37;), and 430 (17&#37;) ALL patients underwent transplantation in first complete remission (CR1), second CR (CR2), third or subsequent CR (CR3 +), and non-CR, respectively. The probabilities of overall survival at 5 years for patients transplanted in CR1, CR2, CR3 + , and non-CR were 58&#37;, 61&#37;, 41&#37;, and 26&#37; for AML patients and 67&#37;, 45&#37;, 20&#37;, and 21&#37; for ALL patients, respectively. Multivariate analyses revealed that the risks of relapse and overall mortality were similar for AML patients transplanted in CR1 and CR2 (P = 0.672 and P = 0.703), whereas they were higher for ALL patients transplanted in CR2 than for those transplanted in CR1 (P < 0.001 for both). The risks of relapse and overall mortality for those transplanted in CR3 + and non-CR increased in a stepwise manner for both diseases, with the relevance being stronger for ALL than for AML patients. These results suggest a significant difference in the effect of disease status at HCT on post-transplant outcomes in AML and ALL. Further investigation to incorporate measurable residual disease data is warranted.

    DOI: 10.1007/s00277-021-04661-2

  • Differential Effect of Graft-versus-Host Disease on Survival in Acute Leukemia according to Donor Type Reviewed International journal

    Konuma, Takaaki; Kanda, Junya; Kuwatsuka, Yachiyo; Yanada, Masamitsu; Kondo, Tadakazu; Hirabayashi, Shigeki; Kako, Shinichi; Akahoshi, Yu; Uchida, Naoyuki; Doki, Noriko; Ozawa, Yukiyasu; Tanaka, Masatsugu; Eto, Tetsuya; Sawa, Masashi; Yoshioka, Satoshi; Kimura, Takafumi; Kanda, Yoshinobu; Fukuda, Takahiro; Atsuta, Yoshiko; Kimura, Fumihiko

    CLINICAL CANCER RESEARCH   27 ( 17 )   4825 - 4835   2021.9

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    Purpose: The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source.

    Experimental design: We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia (n = 6,548) between 2007 and 2017 using a Japanese database. In all analyses, we separately evaluated three distinct cohorts based on donor type [(8/8 allele-matched sibling donor, 8/8 allele-matched unrelated donor, and unrelated single-cord blood (UCB)].

    Results: The multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, showed a reductive effect of grade I-II acute GVHD on treatment failure (defined as 1-leukemia-free survival; P < 0.001), overall mortality (OM; P < 0.001), relapse (P < 0.001), and non-relapse mortality (NRM; P < 0.001) in patients receiving from UCB. A reductive effect of limited chronic GVHD on treatment failure (P < 0.001), OM (P < 0.001), and NRM (P < 0.001) was also shown in patients receiving from UCB. However, these effects were not always shown in patients receiving from other donors. The beneficial effects of mild acute and chronic GVHD after UCB transplantation on treatment failure were noted relatively in subgroups of patients with acute myelogenous leukemia and a non-remission status.

    Conclusions: These data suggested that the development of mild GVHD could improve survival after UCB transplantation for acute leukemia.

    DOI: 10.1158/1078-0432.CCR-20-4856

  • Personalized prediction of overall survival in patients with AML in non-complete remission undergoing allo-HCT Invited Reviewed International journal

    Hirabayashi, Shigeki; Uozumi, Ryuji; Kondo, Tadakazu; Arai, Yasuyuki; Kawata, Takahito; Uchida, Naoyuki; Marumo, Atsushi; Ikegame, Kazuhiro; Fukuda, Takahiro; Eto, Tetsuya; Tanaka, Masatsugu; Wake, Atsushi; Kanda, Junya; Kimura, Takafumi; Tabuchi, Ken; Ichinohe, Tatsuo; Atsuta, Yoshiko; Yanada, Masamitsu; Yano, Shingo

    CANCER MEDICINE   10 ( 13 )   4250 - 4268   2021.7

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    DOI: 10.1002/cam4.3920

  • Comparison of fludarabine, a myeloablative dose of busulfan, and melphalan vs conventional myeloablative conditioning regimen in patients with relapse and refractory acute myeloid leukemia in non-remission status. Reviewed International journal

    Shimomura Y, Hara M, Hirabayashi S, Kondo T, Mizuno S, Uchida N, Mukae J, Kawakita T, Fukuda T, Kanda Y, Ota S, Ozawa Y, Eto T, Maruyama Y, Tanaka M, Yanada M

    Bone marrow transplantation   2021.6

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    DOI: 10.1038/s41409-021-01380-0

  • Differential effect of graft-versus-host disease on survival in acute leukemia according to donor type Reviewed International journal

    Takaaki Konuma, Junya Kanda, Yachiyo Kuwatsuka, Masamitsu Yanada, Tadakazu Kondo, Shigeki Hirabayashi, Shinichi Kako, Yu Akahoshi, Naoyuki Uchida, Noriko Doki, Yukiyasu Ozawa, Masatsugu Tanaka, Tetsuya Eto, Masashi Sawa, Satoshi Yoshioka, Takafumi Kimura, Yoshinobu Kanda, Takahiro Fukuda, Yoshiko Atsuta, Fumihiko Kimura

    Clinical Cancer Research   27 ( 17 )   4825 - 4835   2021.6

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    PURPOSE: The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source. EXPERIMENTAL DESIGN: We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia (n = 6,548) between 2007 and 2017 using a Japanese database. In all analyses, we separately evaluated three distinct cohorts based on donor type [(8/8 allele-matched sibling donor, 8/8 allele-matched unrelated donor, and unrelated single-cord blood (UCB)]. RESULTS: The multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, showed a reductive effect of grade I-II acute GVHD on treatment failure (defined as 1-leukemia-free survival; P < 0.001), overall mortality (OM; P < 0.001), relapse (P < 0.001), and non-relapse mortality (NRM; P < 0.001) in patients receiving from UCB. A reductive effect of limited chronic GVHD on treatment failure (P < 0.001), OM (P < 0.001), and NRM (P < 0.001) was also shown in patients receiving from UCB. However, these effects were not always shown in patients receiving from other donors. The beneficial effects of mild acute and chronic GVHD after UCB transplantation on treatment failure were noted relatively in subgroups of patients with acute myelogenous leukemia and a non-remission status. CONCLUSIONS: These data suggested that the development of mild GVHD could improve survival after UCB transplantation for acute leukemia.

    DOI: 10.1158/1078-0432.CCR-20-4856

  • Residual disease is a strong prognostic marker in patients with acute lymphoblastic leukaemia with chemotherapy‐refractory or relapsed disease prior to allogeneic stem cell transplantation Reviewed International journal

    Momoko Nakamura, Yasuyuki Arai, Shigeki Hirabayashi, Tadakazu Kondo, Noriko Doki, Naoyuki Uchida, Takahiro Fukuda, Yukiyasu Ozawa, Masatsugu Tanaka, Masashi Sawa, Yuta Katayama, Yoshinobu K, a, Souichi Shiratori, Hirohisa Nakamae, Satoshi Yoshioka, Makoto Onizuka, Tatsuo Ichinohe, Yoshiko Atsuta, Shinichi Kako

    British Journal of Haematology   194 ( 2 )   403 - 413   2021.6

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    Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is one of the curative treatment options for acute lymphoblastic leukaemia (ALL). However, the outcomes in patients transplanted without complete remission (non-CR) have not yet been fully reported, and detailed analyses are required to identify subgroups in which optimal prognosis is expected and to optimize pre-transplant therapeutic strategies. Hence, we performed a multicentred retrospective cohort study including a total of 663 adult ALL patients transplanted at non-CR status; the median bone marrow (BM) blast counts at HSCT was 13·2&#37;, and 203 patients (30·6&#37;) were treated at primary induction failure status. The overall survival (OS) was 31·1&#37; at two years, and the multivariate analyses identified five prognostic risk factors, including older age (≥50 years), increased BM blasts (≥10&#37;), poor performance status, high haematopoietic cell transplantation (HCT)-comorbidity index, and relapsed disease status, among which BM blast was the most significantly related. A predictive scoring system composed of these risk factors clearly stratified OS (15·6-59·5&#37; at two years). In conclusion, this is the first large-scale study to analyze the correlation of patient characteristics with post-transplant prognosis in ALL transplanted at non-CR status. The importance of blast control before HSCT should be focused on for better patient prognosis.

    DOI: 10.1111/bjh.17646

  • Identification of candidate PAX2-regulated genes implicated in human kidney development. Reviewed

    Yamamura Y, Furuichi K, Murakawa Y, Hirabayashi S, Yoshihara M, Sako K, Kitajima S, Toyama T, Iwata Y, Sakai N, Hosomichi K, Murphy PM, Tajima A, Wada T

    Scientific reports   11 ( 1 )   2021.4

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    <title>Abstract</title><italic>PAX2</italic> is a transcription factor essential for kidney development and the main causative gene for renal coloboma syndrome (RCS). The mechanisms of PAX2 action during kidney development have been evaluated in mice but not in humans. This is a critical gap in knowledge since important differences have been reported in kidney development in the two species. In the present study, we hypothesized that key human PAX2-dependent kidney development genes are differentially expressed in nephron progenitor cells from induced pluripotent stem cells (iPSCs) in patients with RCS relative to healthy individuals. Cap analysis of gene expression revealed 189 candidate promoters and 71 candidate enhancers that were differentially activated by PAX2 in this system in three patients with RCS with <italic>PAX2</italic> mutations. By comparing this list with the list of candidate Pax2-regulated mouse kidney development genes obtained from the Functional Annotation of the Mouse/Mammalian (FANTOM) database, we prioritized 17 genes. Furthermore, we ranked three genes—<italic>PBX1</italic>, <italic>POSTN</italic>, and <italic>ITGA9</italic>—as the top candidates based on closely aligned expression kinetics with PAX2 in the iPSC culture system and susceptibility to suppression by a Pax2 inhibitor in cultured mouse embryonic kidney explants. Identification of these genes may provide important information to clarify the pathogenesis of RCS, human kidney development, and kidney regeneration.

    DOI: 10.1038/s41598-021-88743-1

  • APOBEC3B is preferentially expressed at the G2/M phase of cell cycle Invited Reviewed International journal

    Hirabayashi S, Shirakawa K, Horisawa Y, Matsumoto T, Matsui H, Yamazaki H, Sarca AD, Kazuma Y, Nomura R, Konishi Y, Takeuchi S, Stanford E, Kawaji H, Murakawa Y, Takaori-Kondo A

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   546   178 - 184   2021.3

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    DOI: 10.1016/j.bbrc.2021.02.008

  • CAGE-seq reveals that HIV-1 latent infection does not trigger unique cellular responses in a Jurkat T cell model. Reviewed

    Matsui H, Shirakawa K, Konishi Y, Hirabayashi S, Sarca AD, Fukuda H, Nomura R, Stanford E, Horisawa Y, Kazuma Y, Matsumoto T, Yamazaki H, Murakawa Y, Takaori-Kondo A

    Journal of virology   95 ( 8 )   2021.1

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    <title>ABSTRACT</title>
    The cure for HIV-1 is currently stalled by our inability to specifically identify and target latently infected cells. HIV-1 viral RNA/DNA or viral proteins are recognized by cellular mechanisms and induce interferon responses in virus-producing cells, but changes in latently infected cells remain unknown. HIVGKO contains a green fluorescent protein (GFP) reporter under the HIV-1 promoter and a monomeric Kusabira orange 2 (mKO2) reporter under the internal elongation factor alpha (EF1α) promoter. This viral construct enables direct identification of both productively and latently HIV-1-infected cells. In this study, we aim to identify specific cellular transcriptional responses triggered by HIV-1 entry and integration using cap analysis of gene expression (CAGE). We deep sequenced CAGE tags in non-infected and latently and productively infected cells and compared their differentially expressed transcription start site (TSS) profiles. Virus-producing cells had differentially expressed TSSs related to T-cell activation and apoptosis compared to those of non-infected cells or latently infected cells. Surprisingly, latently infected cells had only 33 differentially expressed TSSs compared to those of non-infected cells. Among these, SPP1 and APOE were downregulated in latently infected cells. SPP1 or APOE knockdown in Jurkat T cells increased susceptibility to HIVGKO infection, suggesting that they have antiviral properties. Components of the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway, MLST8, 4EBP, and RPS6, were significant TSSs in productively infected cells, and S6 kinase (S6K) phosphorylation was increased compared to that in latently infected cells, suggesting that mTOR pathway activity plays a role in establishing the latent reservoir. These findings indicate that HIV-1 entry and integration do not trigger unique transcriptional responses when infection becomes latent.


    <bold>IMPORTANCE</bold> Latent HIV-1 infection is established as early as the first viral exposure and remains the most important barrier in obtaining the cure for HIV-1 infection. Here, we used cap analysis of gene expression (CAGE) to compare the transcriptional landscape of latently infected cells with that of non-infected or productively infected cells. We found that latently infected cells and non-infected cells show quite similar transcriptional profiles. Our data suggest that T cells cannot recognize incoming viral components or the integrated HIV-1 genome when infection remains latent. These findings should guide future research into widening our approaches to identify and target latent HIV-1-infected cells.

    DOI: 10.1128/jvi.02394-20

  • Measurable residual disease affects allogeneic hematopoietic cell transplantation in Ph+ ALL during both CR1 and CR2 Reviewed International journal

    Satoshi Nishiwaki, Yu Akahoshi, Shuichi Mizuta, Akihito Shinohara, Shigeki Hirabayashi, Yuma Noguchi, Takahiro Fukuda, Naoyuki Uchida, Masatsugu Tanaka, Makoto Onizuka, Yukiyasu Ozawa, Shuichi Ota, Souichi Shiratori, Yasushi Onishi, Yoshinobu Kanda, Masashi Sawa, Junji Tanaka, Yoshiko Atsuta, Shinichi Kako

    Blood Advances   5 ( 2 )   584 - 592   2021.1

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    Although measurable residual disease (MRD) at the time of allogeneic hematopoietic cell transplantation (allo-HCT) has been reported to be an important prognostic factor for Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) during first complete remission (CR1), the prognostic impact of MRD is unclear during second CR (CR2). To clarify the impact of MRD for both CR1 and CR2, we analyzed data from a registry database including 1625 adult patients with Ph+ ALL who underwent first allo-HCT during either CR1 or CR2 between 2002 and 2017. Adjusted overall and leukemia-free survival rates at 4 years were 71&#37; and 64&#37;, respectively, for patients undergoing allo-HCT during CR1 with MRD-, 55&#37; and 43&#37; during CR1 with MRD+, 51&#37; and 49&#37; during CR2 with MRD-, and 38&#37; and 29&#37; during CR2 with MRD+. Although survival rates were significantly better among patients with CR1 MRD- than among patients with CR2 MRD-, no significant difference was observed in survival rate between patients with CR1 MRD+ and CR2 MRD-. Relapse rates after 4 years were 16&#37; in patients with CR1 MRD-, 29&#37; in CR1 MRD+, 21&#37; in patients with CR2 MRD-, and 46&#37; in patients with CR2 MRD+. No significant difference was identified in relapse rate between patients with CR1 MRD- and CR2 MRD-. CR2 MRD- was not a significant risk factor for relapse in multivariate analysis (hazard ratio, 1.26; 95&#37; confidence interval, 0.69-2.29; P = .45 vs CR1 MRD-). MRD at time of allo-HCT was an important risk factor in patients with Ph+ ALL during both CR1 and CR2.

    DOI: 10.1182/bloodadvances.2020003536

  • The impacts of BCR-ABL1 mutations in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent allogeneic hematopoietic cell transplantation. Reviewed International journal

    Tachibana T, Najima Y, Akahoshi Y, Hirabayashi S, Harada K, Doki N, Uchida N, Fukuda T, Sawa M, Ogata M, Takada S, Tanaka M, Matsuhashi Y, Tanaka J, dummy-AUTHOR_name, Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation

    Annals of hematology   99 ( 10 )   2393 - 2404   2020.8

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    The prognostic impacts of BCR-ABL1 fusion gene mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Using data from a nationwide Japanese registry, we have evaluated the prognostic impact of BCR-ABL1 mutations prior to the first allogeneic hematopoietic cell transplantation (HCT). The cohort included 289 patients with a median of 48 years of age (range: 16-70). Point mutations were detected in 110 patients. Of these, 90 (82&#37;) harbored T315I mutations, while 20 had other mutations. With a median follow-up period of 29 months (range: 1-125), outcomes after 2 years were worse with mutations than without (overall survival [OS]: 34&#37; vs 68&#37;, p < 0.001; relapse rate [RR]: 48&#37; vs 18&#37;, p < 0.001), particularly with the presence of the T315I mutation (OS: 29&#37; vs 68&#37;, p < 0.001; RR: 54&#37; vs 18&#37;, p < 0.001). OS was significantly worse in the T315I group even among the cohort with hematological (p < 0.001) or molecular complete remission (p = 0.025) as compared to the no mutation group. Multivariate analysis determined the prognostic impact of the T315I mutation (OS: hazard ratio [HR] = 2.19, 95&#37; confidence interval [CI]: 1.5-3.3, p < 0.001; RR: HR = 2.51, 95&#37; CI: 1.5-4.2, p < 0.001). This study is the first to report on the prognostic significance of BCR-ABL1 mutations in Ph + ALL.

    DOI: 10.1007/s00277-020-04212-1

  • NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements Reviewed International journal

    Hirabayashi S, Bhagat S, Matsuki Y, Takegami Y, Takuya U, Kanemaru A, Itoh M, Shirakawa K, Takaori-Kondo A, Takeuchi O, Carninci P, Katayama S, Hayashizaki Y, Kere J, Kawaji H, Murakawa Y.

    NATURE GENETICS   51 ( 9 )   1369 - +   2019.9

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    DOI: 10.1038/s41588-019-0485-9

  • Endogenous APOBEC3B Overexpression Constitutively Generates DNA Substitutions and Deletions in Myeloma Cells Reviewed International journal

    Hiroyuki Yamazaki, Kotaro Shirakawa, Tadahiko Matsumoto, Shigeki Hirabayashi, Yasuhiro Murakawa, Masayuki Kobayashi, Anamaria Daniela Sarca, Yasuhiro Kazuma, Hiroyuki Matsui, Wataru Maruyama, Hirofumi Fukuda, Ryutaro Shirakawa, Keisuke Shindo, Masaki Ri, Shinsuke Iida, Akifumi Takaori-Kondo

    Scientific Reports   9 ( 1 )   7122 - 7122   2019.5

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    Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) DNA cytosine deaminases have emerged as potential genomic mutators in various cancers. Multiple myeloma accumulates APOBEC signature mutations as it progresses; however, the mechanisms underlying APOBEC signature acquisition and its consequences remain elusive. In this study, we examined the significance and clinical impact of APOBEC3B (A3B) activity in multiple myeloma. Among APOBECs, only highly expressed A3B was associated with poor prognosis in myeloma patients, independent of other known poor prognostic factors. Quantitative PCR revealed that CD138-positive primary myeloma cells and myeloma cell lines exhibited remarkably high A3B expression levels. Interestingly, lentiviral A3B knockdown prevented the generation of deletion and loss-of-function mutations in exogenous DNA, whereas in control cells, these mutations accumulated with time. A3B knockdown also decreased the basal levels of γ-H2AX foci, suggesting that A3B promotes constitutive DNA double-strand breaks in myeloma cells. Importantly, among control shRNA-transduced cells, we observed the generation of clones that harboured diverse mutations in exogenous genes and several endogenous genes frequently mutated in myeloma, including TP53. Taken together, the results suggest that A3B constitutively mutates the tumour genome beyond the protection of the DNA repair system, which may lead to clonal evolution and genomic instability in myeloma.

    DOI: 10.1038/s41598-019-43575-y

  • HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia. Reviewed International journal

    Takiuchi Y, Kobayashi M, Tada K, Iwai F, Sakurada M, Hirabayashi S, Nagata K, Shirakawa K, Shindo K, Yasunaga JI, Murakawa Y, Rajapakse V, Pommier Y, Takaori-Kondo A

    Scientific reports   7 ( 1 )   12849 - 12849   2017.10

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    Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). We recently reported that abacavir, an anti-HIV-1 drug, potently and selectively kills ATL cells. This effect was attributed to the reduced expression of tyrosyl-DNA-phosphodiesterase 1 (TDP1), a DNA repair enzyme, in ATL cells. However, the molecular mechanism underlying the downregulation of TDP1 in ATL cells remains elusive. Here we identified the core promoter of the TDP1 gene, which contains a conserved nuclear respiratory factor 1 (NRF-1) binding site. Overexpression of NRF-1 increased TDP1-promoter activity, whereas the introduction of dominant-negative NRF-1 repressed such activity. Overexpression of NRF-1 also upregulated endogenous TDP-1 expression, while introduction of shNRF-1 suppressed TDP1 in Jurkat T cells, making them susceptible to abacavir. These results indicate that NRF-1 is a positive transcriptional regulator of TDP1-gene expression. Importantly, we revealed that HTLV-1 bZIP factor (HBZ) protein which is expressed in all ATL cases physically interacts with NRF-1 and inhibits the DNA-binding ability of NRF-1. Taken together, HBZ suppresses TDP1 expression by inhibiting NRF-1 function in ATL cells. The HBZ/NRF-1/TDP1 axis provides new therapeutic targets against ATL and might explain genomic instability leading to the pathogenesis of ATL.

    DOI: 10.1038/s41598-017-12924-0

  • Gastric cancer treated by endoscopic submucosal dissection or endoscopic mucosal resection in Japan from 2004 through 2006: JGCA nationwide registry conducted in 2013. Reviewed

    Tanabe S, Hirabayashi S, Oda I, Ono H, Nashimoto A, Isobe Y, Miyashiro I, Tsujitani S, Seto Y, Fukagawa T, Nunobe S, Furukawa H, Kodera Y, Kaminishi M, Katai H

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association   20 ( 5 )   834 - 842   2017.9

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    BACKGROUND: The Japanese Gastric Cancer Association (JGCA) initiated a new nationwide gastric cancer registry in 2008 and reported the treatment outcomes of patients with primary gastric cancer who underwent surgical therapy in 2001 and 2003. However, the outcomes of endoscopic therapy have not been reported yet. METHODS: The JGCA conducted a retrospective nationwide registry in 2013 to investigate the short-term and long-term outcomes of endoscopic mucosal resection or endoscopic submucosal dissection in patients with gastric cancer treated from January 2004 through December 2006. This registry used a computerized database with terminology in accordance with the JGCA classification (13th and 14th editions) and the Japanese Gastric Cancer Treatment Guidelines from 2010. RESULTS: Accurate data on 12,647 patients were collected from 126 participating hospitals and analyzed. The treatment procedure was endoscopic submucosal dissection in 81&#37; of the patients and endoscopic mucosal resection in 19&#37;. En bloc and R0 resections were achieved in 89&#37; and 79&#37; of the patients respectively. The total proportion of patients who underwent curative resection was 69.2&#37;; 43.8&#37; of patients underwent curative resection for absolute indication lesions, and 25.4&#37; underwent curative resection for expanded indication lesions. Emergency surgery was performed to treat bleeding or perforation in very few patients (0.3&#37; and 0.4&#37; respectively). The 5-year follow-up rate after endoscopic resection was 70&#37;. The 5-year overall survival rate was 91.6&#37; in patients with absolute indications and 90.3&#37; in patients with expanded indications after curative resection and 86.5&#37; in patients who underwent noncurative resection. The 5-year disease-specific survival rates were 99.9&#37;, 99.7&#37;, and 98.7&#37; in patients with absolute indications who underwent curative resection, patients with expanded indications who underwent curative resection, and patients who underwent noncurative resection respectively. CONCLUSION: Endoscopic resection of gastric cancer resulted in favorable short-term and long-term outcomes nationwide in Japan. Further efforts to increase the follow-up rate are needed.

    DOI: 10.1007/s10120-017-0699-4

  • Successful treatment of severe acute gastrointestinal graft-versus-host disease complicated by cytomegalovirus gastroenteritis with intra-arterial steroid infusion Invited Reviewed International journal

    Hirabayashi, Shigeki; Kondo, Tadakazu; Oka, Tomomi; Akamatsu, Yuri; Hishizawa, Masakatsu; Shibata, Toshiya; Kitano, Toshiyuki; Takaori-Kondo, Akifumi

    ANNALS OF HEMATOLOGY   95 ( 8 )   1373 - 1375   2016.8

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    DOI: 10.1007/s00277-016-2686-y

  • Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer Reviewed International journal

    Hirabayashi S, Kosugi S, Isobe Y, Nashimoto A, Oda I, Hayashi K, Miyashiro I, Tsujitani S, Kodera Y, Seto Y, Furukawa H, Ono H, Tanabe S, Kaminishi M, Nunobe S, Fukagawa T, Matsuo R, Nagai T, Katai H, Wakai T, Akazawa K.

    ANNALS OF ONCOLOGY   25 ( 6 )   1179 - 1184   2014.6

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    DOI: 10.1093/annonc/mdu125

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Presentations

MISC

  • 複数のHLA座不適合が単一臍帯血移植後の成績に与える影響 JSTCT HLA WG研究

    諫田 淳也, 平林 茂樹, 横山 寿行, 川瀬 孝和, 田中 秀則, 内田 直之, 谷口 修一, 高橋 聡, 鬼塚 真仁, 田中 正嗣, 杉尾 康浩, 衛藤 徹也, 神田 善伸, 木村 貴文, 一戸 辰夫, 熱田 由子, 森島 聡子

    MHC: Major Histocompatibility Complex   2021.9

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    Language:Japanese  

  • miRNAの発現と疾患の関わり

    平林 茂樹, 廣瀬 直毅, Michiel de Hoon

    医学のあゆみ   2019.4

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  • Cap Analysis of Gene Expression

    平林 茂樹, 村川 泰裕

    腎臓内科・泌尿器科   2017.1

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    Cap Analysis of Gene Expression

Professional Memberships

  • 日本血液学会

  • 日本内科学会

  • 日本癌学会

  • 日本造血・免疫細胞療法学会

  • 日本バイオインフォマティクス学会

  • 日本臨床腫瘍学会

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Committee Memberships

  • 九州大学   医学部教育主任  

    2022 - Present   

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    Committee type:Other

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Other

  • OSCE認定評価者

    2023 - Present

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  • 日本造血・免疫細胞療法学会認定医

    2022 - Present

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  • 日本血液学会専門医

    2018 - Present

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  • 日本内科学会認定医

    2016 - Present

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Research Projects

  • 遺伝性血液腫瘍の変異が病態に及ぼす本質的な意義の解明

    Grant number:24K18518  2024 - 2025

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Early-Career Scientists

    平林 茂樹

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    Authorship:Principal investigator  Grant type:Scientific research funding

    急性骨髄性白血病/ 骨髄異形成症候群(AML/MDS)の原因遺伝子として、ATP依存性RNAヘリカーゼであるDDX41が同定された。DDX41変異を有するAML/MDS患者は、胚細胞変異としてA500fs、D140fsのような機能喪失型の変異を有し、後天的にR525Hを主とした体細胞変異を対側アリルに獲得し、AML/MDSを発症することが多い。近年DDX41変異を有するAML/MDSの発症・維持機構に関して様々な知見が得られているが、まだ十二分ではない。本研究では、DDX41変異がAML/MDSに果たす役割を解明することを目的として研究を行う。

    CiNii Research

  • 遺伝性血液腫瘍の発症に関わる病的バリアントの網羅的な同定

    2023 - 2025

    日本医療研究開発機構

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    Authorship:Principal investigator  Grant type:Contract research

  • 遺伝性免疫不全疾患のVUSへの機能的アノテーションに資する網羅的CRISPR塩基編集法の開発

    2023 - 2025

    日本医療研究開発機構

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    Authorship:Principal investigator  Grant type:Contract research

  • KRAS標的治療の抵抗性に関与するKRAS変異の網羅的同定

    2023 - 2024

    日本医療研究開発機構

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    Authorship:Principal investigator  Grant type:Contract research

  • 大規模ゲノミクスと機能的スクリーニングに基づく新規がん治療標的の探索

    2022.6

  • 大規模ゲノミクスと機能的スクリーニングに基づく新規がん治療標的の探索

    Grant number:22K16323  2022 - 2023

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Early-Career Scientists

    平林 茂樹

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    Authorship:Principal investigator  Grant type:Scientific research funding

    近年のゲノム解析の進展により、血液腫瘍・がんの発症・維持に関与する遺伝子異常が複数同定され、それらに対する分子標的薬が開発されてきた。しかし、腫瘍に多様なクローンが存在するために、一部のクローンを分子標的薬で駆逐しても治療抵抗性の他のクローンが増殖し、根治がしばしば困難である。それゆえ、今なお従来の化学療法が欠かせないものとなっている。したがって、本研究ではがん細胞と正常細胞の生存に必須な遺伝子を同定することで、重篤な有害事象を抑えながらも血液腫瘍を主とした多彩ながんに奏功する新規治療法の開発を目指す。

    CiNii Research

  • 大規模ゲノミクスと機能的スクリーニングに基づく新規がん治療標的の探索

    2022 - 2023

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Early-Career Scientists

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    Grant type:Scientific research funding

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Class subject

  • 生命の科学A

    2023.4 - 2023.9   First semester

  • 医学部実習講義

    2022.4 - 2022.9   First semester

Travel Abroad

  • 2012.4 - 2012.5

    Staying countory name 1:United States   Staying institution name 1:University of California, Davis

  • 2010.8 - 2010.11

    Staying countory name 1:United States   Staying institution name 1:University of Massachusetts

  • 2008.8 - 2008.9

    Staying countory name 1:Russian Federation   Staying institution name 1:Far Eastern State Medical University

Specialized clinical area

  • Biology / Medicine, Dentistry and Pharmacy / Internal Medicine / Hematology

Clinician qualification

  • Certifying physician

    The Japanese Society of Internal Medicine(JSIM)

  • Specialist

    The Japanese Society of Hematology

  • Certifying physician

    日本造血・免疫細胞療法学会

Year of medical license acquisition

  • 2013