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Nakagawa Masao

Hokkaido University Hospital　Internal MedicineLecturer
Hokkaido University HospitalLecturer

Researcher basic information

■ Degree
  • MD. Ph.D., Hokkaido University
■ URL
researchmap URLホームページURL■ Various IDs
J-Global ID■ Research Keywords and Fields
Research Keyword
  • Immunotherapy
  • Oncology
  • Immunology
  • Lymphoma
Research Field
  • Life Science, Hematology and medical oncology
■ Educational Organization

Research activity information

■ Awards
  • 2108, The Princess Takamatsu Cancer Research Fund,, Research Grant
    全ゲノムCRISPRスクリーニング法を用いたT細胞性リンパ腫に対する新規免疫療法の探索
    Masao Nakagawa
  • 2019, Nagoya International Cancer Treatment Symposium, BMS Award
    Masao Nakagawa
  • 2018, Research Award from Leukemia Research Fund
    Masao Nakagawa
  • 2016, The Fellows Award for Research Excellence (FARE) Travel Award
    Masao Nakagawa
  • 2015, The Center for Cancer Research (CCR) Federal Technology Transfer Award
    Masao Nakagawa
  • 2010, Research Fellowship of Uehara Memorial Foundation
    Masao Nakagawa
■ Papers
  • Correction: Genome-wide CRISPR screen identifies MAD2L1BP and ANAPC15 as targets for brentuximab vedotin sensitivity in CD30+ peripheral T-cell lymphoma.
    Keito Suto; Norio Takei; Keito Yokoyama; Masahiro Chiba; Takashi Ishio; Michiyuki Maeda; Hideki Goto; Tomoyuki Endo; Takanori Teshima; Yibin Yang; Masao Nakagawa
    Leukemia, 10 Nov. 2025, [International Magazine]
    English
  • Safety and Efficacy of Graft-versus-Host Disease Prophylaxis with Mini-Dose Methotrexate in Umbilical Cord Blood Transplantation: An NJHSG-CBT18 Observational Study.
    Souichi Shiratori; Keito Suto; Yuta Hasegawa; Takahide Ara; Toshihiro Matsukawa; Hideki Goto; Masahiro Onozawa; Masao Nakagawa; Kaoru Kahata; Daisuke Hidaka; Reiki Ogasawara; Kohei Okada; Junichi Sugita; Yasutaka Kakinoki; Shuichi Ota; Daigo Hashimoto; Takanori Teshima
    Transplantation and cellular therapy, 06 Nov. 2025, [International Magazine]
    English, Scientific journal, Tacrolimus (Tac) and methotrexate (MTX) are standard graft-versus-host disease (GVHD) prophylaxis for umbilical cord blood transplantation (CBT); however, the optimal dose of MTX for CBT remains to be determined. We previously showed the safety and efficacy of reduced-dose MTX (mini-MTX; 5 mg/m2 on days 1, 3, and 6) combined with Tac as GVHD prophylaxis for CBT in a single-center retrospective study. Here we report a multicenter observational study in the North Japan Hematology Study Group (NJHSG; NJHSG-CBT18) conducted to evaluate transplantation outcomes according to GVHD prophylaxis in single-unit CBT, in which patients with hematologic malignancies scheduled for CBT were prospectively registered and followed for 2 years after CBT. A total of 112 patients were registered in NJHSG-CBT18, with a median age of 51 years. Eighty-nine patients received Tac + mini-MTX, 19 patients received Tac + mycophenolate mofetil (MMF), and 4 patients received Tac only as GVHD prophylaxis. Multivariate analysis identified GVHD prophylaxis other than Tac + mini-MTX as a significant risk factor for nonrelapse mortality (NRM) (hazard ratio [HR], 0.160; 95% confidence interval [CI], 0.065 to 0.391; P < .001), overall survival (OS) (HR, 2.971; 95% CI, 1.558 to 5.663; P < .001), progression-free survival (PFS) (HR, 2.383; 95% CI, 1.345 to 4.222; P = .003), and GVHD-free, relapse-free survival (GRFS) (HR, 3.075; 95% CI, 1.799 to 5.256; P < .001). In a comparison of clinical outcomes between the mini-MTX and MMF groups, the cumulative incidences of pre-engraftment immune reaction (5.7% versus 42.1%; P < .001), human herpesvirus 6 encephalitis (2.3% versus 15.8%, P = .011), grade II-IV acute GVHD (14.6% versus 47.4%, P < .001), and NRM (1.1% versus 52.6%, P < .001) were significantly lower and the cumulative incidence of immunosuppressant discontinuation was significantly higher (66.3% versus 18.4%, P = .004) in the mini-MTX group compared to the MMF group, while rates of chronic GVHD and relapse were comparable between the groups. The probabilities of OS (70.6% versus 31.6%, P < .001), PFS (58.1 versus 14.0%, P < .001), and GRFS (44.9% versus 5.1%, P < .001) were significantly higher in the mini-MTX group. Multivariate analysis of risk factors for OS in the mini-MTX group identified high-risk or very high-risk refined Disease Risk Index (rDRI) (HR, 3.896; 95% CI, 1.575 to 9.637; P = .003) and high HCT-CI (HR, 3.338; 95% CI, 1.301 to 8.569; P = .012) as significant risk factors for OS. Our data indicate that a combination of Tac + mini-MTX is safe and effective GVHD prophylaxis in CBT.
  • HLA半合致移植を施行したShwachman-Diamond症候群(SDS)を背景とした急性骨髄性白血病
    塚本 しほり; 中川 雅夫; 小野澤 真弘; 南谷 泰仁; 小島 圭祐; 原田 知弥; 荒 隆英; 松川 敏大; 白鳥 聡一; 遠藤 知之; 豊嶋 崇徳
    臨床血液, 65, 10, 1329, 1329, (一社)日本血液学会-東京事務局, Oct. 2024
    Japanese
  • Whole genome CRISPR screening identifies molecular mechanisms of PD-L1 expression in Adult T-cell leukemia/lymphoma.
    Masahiro Chiba; Joji Shimono; Keito Suto; Takashi Ishio; Tomoyuki Endo; Hideki Goto; Hiroo Hasegawa; Michiyuki Maeda; Takanori Teshima; Yibin Yang; Masao Nakagawa
    Blood, 24 Dec. 2023, [International Magazine]
    English, Scientific journal, Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis and limited treatment options. Programmed cell death ligand 1(PD-L1) is recognized to be involved in the pathobiology of ATLL. However, what molecules control PD-L1 expression and whether genetic or pharmacological intervention might modify PD-L1 expression in ATLL cells is still unknown. In order to comprehend the regulatory mechanisms of PD-L1 expression in ATLL cells, we performed unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening in this work. In ATLL cells, we discovered that the neddylation-associated genes NEDD8, NAE1, UBA3, and CUL3 negatively regulated PD-L1 expression while STAT3 positively did so in ATLL cells. We verified, in line with the genetic results, that treatment with the JAK1/2 inhibitor ruxolitinib or the neddylation pathway inhibitor pevonedistat resulted in a decrease in PD-L1 expression in ATLL cells or an increase in it. It is significant that these results held true regardless of whether ATLL cells had the PD-L1 3' structural variant, a known genetic anomaly that promotes PD-L1 overexpression in certain primary ATLL patients. Pevonedistat alone showed cytotoxicity for ATLL cells, but compared to each single modality, pevonedistat improved the cytotoxic effects of the anti-PD-L1 monoclonal antibody Avelumab and chimeric antigen receptor T-cells targeting PD-L1 in vitro. As a result, our work provided insight into a portion of the complex regulatory mechanisms governing PD-L1 expression in ATLL cells and demonstrated the in vitro preliminary preclinical efficacy of PD-L1-directed immunotherapies by using pevonedistat to upregulate PD-L1 in ATLL cells.
  • Incidence and course of Epstein-Barr virus viremia after allogeneic hematopoietic stem cell transplant for adult-onset systemic chronic active Epstein-Barr virus disease.
    Preeti Prerna M Vaswani; Masahiro Onozawa; Yuta Hasegawa; Hiroyuki Ohigashi; Takahide Ara; Toshihiro Matsukawa; Atsushi Yasumoto; Souichi Shiratori; Hideki Goto; Masao Nakagawa; Kaoru Kahata; Tomoyuki Endo; Daigo Hashimoto; Takanori Teshima
    Bone marrow transplantation, 05 Sep. 2023, [International Magazine]
    English
  • 大腿骨人工骨頭インプラント周囲に発症したALK陰性未分化大細胞型リンパ腫の1例
    森 祐斗; 荒 隆英; 中川 雅夫; 吉田 匠汰; 斎藤 祐美花; 横山 翔大; 松川 敏大; 白鳥 聡一; 遠藤 知之; 豊嶋 崇徳
    臨床血液, 63, 11, 1592, 1593, (一社)日本血液学会-東京事務局, Nov. 2022
    Japanese
  • Antiretroviral therapy achieved metabolic complete remission of hepatic AIDS related Epstein-Barr virus-associated smooth muscle tumor.
    Takahide Ara; Tomoyuki Endo; Hideki Goto; Kohei Kasahara; Yuta Hasegawa; Shota Yokoyama; Souichi Shiratori; Masao Nakagawa; Ken Kuwahara; Emi Takakuwa; Satoshi Hashino; Takanori Teshima
    Antiviral therapy, 27, 5, 13596535221126828, 13596535221126828, Oct. 2022, [International Magazine]
    English, Scientific journal, Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor which occurs in immunocompromised patients. The immune status is an important factor in the treatment of EBV-SMTs, but the efficacy of antiretroviral therapy (ART) is not elucidated in acquired immune deficiency syndrome (AIDS) related EBV-SMTs. Here, we report the first successful case of a 29-year-old man with hepatic AIDS related EBV-SMT treated with ART solely. Positron emission tomography scan was useful for the evaluation of disease status. Recent advances in ART that enables to restore patient's immune status rapidly may change the treatment strategy in AIDS related EBV-SMT.
  • Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas.
    Masahiro Chiba; Joji Shimono; Takashi Ishio; Norio Takei; Kohei Kasahara; Reiki Ogasawara; Takahide Ara; Hideki Goto; Koh Izumiyama; Satoko Otsuguro; Liyanage P Perera; Hiroo Hasegawa; Michiyuki Maeda; Satoshi Hashino; Katsumi Maenaka; Takanori Teshima; Thomas A Waldmann; Yibin Yang; Masao Nakagawa
    Blood, 140, 18, 1951, 1963, 03 Aug. 2022, [International Magazine]
    English, Scientific journal, Adult T-cell leukemia/lymphoma (ATLL) is one of the aggressive peripheral T-cell neoplasms with a poor prognosis. Accumulating evidence demonstrates that escape from adaptive immunity is a hallmark for ATLL pathogenesis. However, the mechanisms by which ATLL cells evade NK-cell-mediated immunity have been poorly understood. Here we show that CD48 expression in ATLL cells determines the sensitivity for NK-cell-mediated cytotoxicity against ATLL cells. We performed unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening using two ATLL derived cell lines and discovered CD48 as one of the best enriched genes whose knockout conferred resistance to YT-1 NK cell line mediated cytotoxicity. The ability of CD48-knockout ATLL cells to evade NK cell effector function was confirmed using human primary NK cells with reduced IFNg induction and degranulation. We found that primary ATLL cells had reduced CD48 expression along with disease progression. Furthermore, other subgroups among aggressive peripheral T-cell lymphomas (PTCL) also expressed lower levels of CD48 than normal T-cells, suggesting that CD48 is a key molecule in malignant T-cell evasion of NK cell surveillance. Thus, this study demonstrates that CD48 expression is likely critical for malignant T-cell lymphoma cell regulation of NK cell mediated immunity and provides a rationale for future evaluation of CD48 as a molecular biomarker in NK cell-associated immunotherapies.
  • Gilteritinib enhances graft-versus-leukemia effects against FLT3-ITD mutant leukemia after allogeneic hematopoietic stem cell transplantation.
    Zixuan Zhang; Yuta Hasegawa; Daigo Hashimoto; Hajime Senjo; Ryo Kikuchi; Xuanzhong Chen; Kazuki Yoneda; Tomoko Sekiguchi; Tatsuya Kawase; Hirofumi Tsuzuki; Takashi Ishio; Takahide Ara; Hiroyuki Ohigashi; Masao Nakagawa; Takanori Teshima
    Bone marrow transplantation, 57, 5, 775, 780, May 2022, [International Magazine]
    English, Scientific journal, Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative therapy for FLT3 internal tandem duplication mutant (FLT3-ITD+) acute myeloid leukemia, but relapse rate is high. A recent study showed that sorafenib, a first generation FLT3 and multikinase inhibitor, enhanced graft-versus-leukemia (GVL) effects against FLT3-ITD+ leukemia via interleukin-15 (IL-15) production. However, it remains to be clarified whether this effect could be mediated by selective FLT3 inhibition. We investigated whether gilteritinib, a selective FLT3 inhibitor, could enhance GVL effects against FLT3-ITD transfected Ba/F3 leukemia (Ba/F3-FLT3-ITD) in mice. Oral administration of gilteritinib from day +5 to +14 after allo-SCT reduced expression of the co-inhibitory receptors PD-1 and TIGIT on donor CD8+ T cells and enhanced IL-15 expression in Ba/F3-FLT3-ITD. Bioluminescent imaging using luciferase-transfected Ba/F3-FLT3-ITD demonstrated that gilteritinib significantly suppressed leukemia expansion after allo-SCT, whereas it did not impact the morbidity or mortality of graft-versus-host disease (GVHD), resulting in significant improvement of overall survival. In conclusion, short-term administration of gilteritinib after allo-SCT enhanced GVL effects against FLT3-ITD+ leukemia without exacerbating GVHD.
  • Genome-wide CRISPR screen identifies CDK6 as a therapeutic target in Adult T-cell leukemia/lymphoma.
    Takashi Ishio; Sarvesh Kumar; Joji Shimono; Anusara Daenthanasanmak; Sigrid Dubois; Yuquan Lin; Bonita R Bryant; Michael N Petrus; Emmanuel Bachy; Da Wei Huang; Yandan Yang; Patrick L Green; Hiroo Hasegawa; Michiyuki Maeda; Hideki Goto; Tomoyuki Endo; Takashi Yokota; Kanako C Hatanaka; Yutaka Hatanaka; Shinya Tanaka; Yoshihiro Matsuno; Yibin Yang; Satoshi Hashino; Takanori Teshima; Thomas A Waldmann; Louis M Staudt; Masao Nakagawa
    Blood, 139, 10, 1541, 1556, 24 Nov. 2021, [International Magazine]
    English, Scientific journal, Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis with current therapy. Here we report genome-wide CRISPR-Cas9 screening of ATLL models, which identified CDK6, CCND2, BATF3, JUNB, STAT3, and IL10RB as genes that are essential for the proliferation and/or survival of ATLL cells. As a single agent, the CDK6 inhibitor palbociclib induced cell cycle arrest and apoptosis in ATLL models with wild type TP53. ATLL models that had inactivated TP53 genetically were relatively resistant to palbociclib owing to compensatory CDK2 activity, and this resistance could be reversed by APR-246, a small molecule activator of mutant TP53. The CRISPR-Cas9 screen further highlighted the dependence of ATLL cells on mTORC1 signaling. Treatment of ATLL cells with palbociclib in combination with mTORC1 inhibitors was synergistically toxic irrespective of the TP53 status. This work defines CDK6 as a novel therapeutic target for ATLL and supports the clinical evaluation of palbociclib in combination with mTORC1 inhibitors in this recalcitrant malignancy.
  • High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease.
    Souichi Shiratori; Hiroyuki Ohigashi; Takahide Ara; Atsushi Yasumoto; Hideki Goto; Masao Nakagawa; Junichi Sugita; Masahiro Onozawa; Kaoru Kahata; Tomoyuki Endo; Daigo Hashimoto; Takanori Teshima
    Annals of hematology, 100, 5, 1321, 1328, May 2021, [International Magazine]
    English, Scientific journal, Antithymocyte globulin (ATG) reduces severe acute and chronic graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT). However, risk factors for severe acute GVHD in PBSCT using ATG remain to be determined. We conducted a single-center, retrospective study to analyze the association of acute GVHD requiring systemic corticosteroid (SC-aGVHD) with absolute lymphocyte counts (ALC) before the administration of ATG or conditioning in 53 patients with HLA-matched PBSCT using low-dose thymoglobulin (2 mg/kg) after myeloablative conditioning. The cumulative incidence of SC-aGVHD was 17.0% and ALC before ATG were significantly higher in patients with SC-aGVHD compared to that in patients without it (median, 0.15 × 109/L vs 0.06 × 109/L, P = 0.047). The cumulative incidence of SC-aGVHD was significantly higher in patients with high ALC before ATG (≥ 0.15 × 109/L) than in those with low ALC (38.5% vs 10.0%, P = 0.016). Non-relapse mortality (NRM) was also significantly higher in the high ALC before ATG group than the low ALC before ATG group (2-year NRM: 23.9% vs 6.0%, P = 0.048), leading to worse survival (2-year overall survival: 69.2% vs 83.5%, P = 0.039). Our study suggested that high ALC before ATG is a risk factor for SC-aGVHD.
  • A novel model of alternative NF-κB pathway activation in anaplastic large cell lymphoma.
    Hongbo Wang; Wei Wei; Jing-Ping Zhang; Zhihui Song; Yangyang Li; Wenming Xiao; Yijun Liu; Mu-Sheng Zeng; Michael N Petrus; Craig J Thomas; Marshall E Kadin; Masao Nakagawa; Thomas A Waldmann; Yibin Yang
    Leukemia, 12 Nov. 2020, [International Magazine]
    English, Scientific journal, Aberrant activation of NF-κB is the most striking oncogenic mechanism in B-cell lymphoma; however, its role in anaplastic large cell lymphomas (ALCL) has not been fully established and its activation mechanism(s) remain unclear. Using ALCL cell line models, we revealed the supporting roles for NFKB2 and the NIK pathway in some ALCL lines. To investigate the detailed activation mechanisms for this oncogenic pathway, we performed specifically designed alternative NF-κB reporter CRISPR screens followed by the RNA-seq analysis, which led us to identify STAT3 as the major mediator for NIK-dependent NF-κB activation in ALCL. Consistently, p-STAT3 level was correlated with NFKB2 nuclear accumulation in primary clinical samples. Mechanistically, we found that in NIK-positive ALK- ALCL cells, common JAK/STAT3 mutations promote transcriptional activity of STAT3 which directly regulates NFKB2 and CD30 expression. Endogenous expression of CD30 induces constitutive NF-κB activation through binding and degrading of TRAF3. In ALK+ ALCL, the CD30 pathway is blocked by the NPM-ALK oncoprotein, but STAT3 activity and resultant NFKB2 expression can still be induced by NPM-ALK, leading to minimal alternative NF-κB activation. Our data suggest combined NIK and JAK inhibitor therapy could benefit patients with NIK-positive ALK- ALCL carrying JAK/STAT3 somatic mutations.
  • Short-term treatment with imetelstat sensitizes hematopoietic malignant cells to a genotoxic agent via suppression of the telomerase-mediated DNA repair process.
    Daisuke Hidaka; Masahiro Onozawa; Naohiro Miyashita; Shota Yokoyama; Masao Nakagawa; Daigo Hashimoto; Takanori Teshima
    Leukemia & lymphoma, 61, 11, 2722, 2732, Nov. 2020, [International Magazine]
    English, Scientific journal, Imetelstat is a specific and competitive inhibitor of telomerase enzymatic activity. We demonstrated that imetelstat could interfere with the DNA repair process and enhance the effect of DNA damaging agents using hematological tumor cell lines. Short-term administration of imetelstat enhanced growth suppression by anticancer agents and radiation. It also upregulated γH2AX expression induced by irradiation. Immunofluorescence staining showed that both human telomerase reverse transcriptase (hTERT) and γH2AX were upregulated and co-localized in the nucleus of peripheral blood mononuclear cells after irradiation, suggesting that hTERT was involved in the DNA-DSB repair process. Imetelstat enhanced growth inhibitory effect of cytotoxic agents in short-term culture without shortening of telomeres, indicating that this effect was attributed by telomere length independent mechanism. Our results suggest that the combination of short-term treatment with imetelstat and cytotoxic agent is a promising strategy to treat a wide variety of hematopoietic malignancies.
  • Reduced dose of MTX for GVHD prophylaxis promotes engraftment and decreases non-relapse mortality in umbilical cord blood transplantation
    Souichi Shiratori; Hiroyuki Ohigashi; Shuichiro Takahashi; Takahide Ara; Hideki Goto; Masao Nakagawa; Junichi Sugita; Masahiro Onozawa; Kaoru Kahata; Tomoyuki Endo; Daigo Hashimoto; Takanori Teshima
    Annals of Hematology, 99, 3, 591, 598, Springer Science and Business Media LLC, Mar. 2020
    Scientific journal
  • A novel model of controlling PD-L1 expression in ALK+ anaplastic large cell lymphoma revealed by CRISPR screening
    Jing-Ping Zhang; Zhihui Song; Hong-Bo Wang; Lang Lang; Yuan-Zhong Yang; Wenming Xiao; Daniel E. Webster; Wei Wei; Stefan K. Barta; Marshall E. Kadin; Louis M. Staudt; Masao Nakagawa; Yibin Yang
    Blood, 134, 2, 171, 185, American Society of Hematology, 11 Jul. 2019, [Peer-reviewed], [Corresponding author]
    Scientific journal, Abstract
    The success of programmed cell death protein 1 (PD-1)/PD-L1-based immunotherapy highlights the critical role played by PD-L1 in cancer progression and reveals an urgent need to develop new approaches to attenuate PD-L1 function by gaining insight into how its expression is controlled. Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALK+ ALCL) expresses a high level of PD-L1 as a result of the constitutive activation of multiple oncogenic signaling pathways downstream of ALK activity, making it an excellent model in which to define the signaling processes responsible for PD-L1 upregulation in tumor cells. Here, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 library screening, we sought a comprehensive understanding of the molecular effectors required for PD-L1 regulation in ALK+ ALCL. Indeed, we determined that PD-L1 induction is dependent on the nucleophosmin-ALK oncoprotein activation of STAT3, as well as a signalosome containing GRB2/SOS1, which activates the MEK-ERK and PI3K-AKT signaling pathways. These signaling networks, through STAT3 and the GRB2/SOS1, ultimately induce PD-L1 expression through the action of transcription factors IRF4 and BATF3 on the enhancer region of the PD-L1 gene. IRF4 and BATF3 are essential for PD-L1 upregulation, and IRF4 expression is correlated with PD-L1 levels in primary ALK+ ALCL tissues. Targeting this oncogenic signaling pathway in ALK+ ALCL largely inhibited the ability of PD-L1-mediated tumor immune escape when cocultured with PD-1-positive T cells and natural killer cells. Thus, our identification of this previously unrecognized regulatory hub not only accelerates our understanding of the molecular circuitry that drives tumor immune escape but also provides novel opportunities to improve immunotherapeutic intervention strategies.
  • Ocular instillation of vitamin A–coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD
    Hiroyuki Ohigashi; Daigo Hashimoto; Eiko Hayase; Shuichiro Takahashi; Takahide Ara; Tomohiro Yamakawa; Junichi Sugita; Masahiro Onozawa; Masao Nakagawa; Takanori Teshima
    Blood Advances, 3, 7, 1003, 1010, American Society of Hematology, 09 Apr. 2019, [Peer-reviewed]
    Scientific journal, Abstract
    Chronic graft-versus-host disease (GVHD) profoundly affects the quality of life of long-term survivors of allogeneic hematopoietic stem cell transplantation (SCT). The eyes are frequently involved, and dry eye syndrome is the most common manifestation of ocular chronic GVHD. We explored the role of heat shock protein 47 (HSP47) in ocular GVHD and developed a novel antifibrotic topical therapy using vitamin A–coupled liposomes containing HSP47 small interfering RNA (siRNA) against HSP47 (VA-lip HSP47). In a mouse model of chronic GVHD, infiltration of HSP47+ fibroblasts and massive fibrosis surrounding the lacrimal ducts were observed after allogeneic SCT, leading to impaired tear secretion. After ocular instillation, VA-lip HSP47 was distributed to the lacrimal glands, knocked down HSP47 expression in fibroblasts, reduced collagen deposition, and restored tear secretion after allogeneic SCT. Ocular instillation of VA-lip HSP47 also ameliorated established lacrimal gland fibrosis and dry eye syndrome. VA-lip HSP47 eye drops are a promising prophylactic and therapeutic option against dry eye syndrome in chronic GVHD.
  • Wilms Tumor 1 Expression at Diagnosis Correlates With Genetic Abnormalities and Polymorphism But Is Not Independently Prognostic in Acute Myelogenous Leukemia: A Hokkaido Leukemia Net Study.
    Daisuke Hidaka; Masahiro Onozawa; Junichi Hashiguchi; Naohiro Miyashita; Kohei Kasahara; Shinichi Fujisawa; Eiko Hayase; Kohei Okada; Souichi Shiratori; Hideki Goto; Junichi Sugita; Masao Nakagawa; Daigo Hashimoto; Kaoru Kahata; Tomoyuki Endo; Satoshi Yamamoto; Yutaka Tsutsumi; Yoshihito Haseyama; Takahiro Nagashima; Akio Mori; Shuichi Ota; Hajime Sakai; Toshimichi Ishihara; Kiyotoshi Imai; Takuto Miyagishima; Yasutaka Kakinoki; Mitsutoshi Kurosawa; Hajime Kobayashi; Hiroshi Iwasaki; Chikara Shimizu; Takeshi Kondo; Takanori Teshima
    Clinical lymphoma, myeloma & leukemia, 18, 11, e469-e479, Nov. 2018, [International Magazine]
    English, Scientific journal, BACKGROUND: The prognostic effect of Wilms tumor 1 (WT1) expression at the diagnosis of acute myelogenous leukemia (AML) has been controversial. The aim of the present study was to determine the correlations of WT1 expression at the diagnosis of AML with established prognostic alterations. PATIENTS AND METHODS: We analyzed diagnostic bone marrow samples from 252 patients. WT1 expression, single nucleotide polymorphism (SNP) in the WT1 gene (rs16754), and Fms-like tyrosine kinase receptor-3 internal tandem duplication (FLT3-ITD) mutation were analyzed for all patients. The nucleophosmin 1 (NPM1) mutation and CCAAT/enhancer-binding protein-α (CEBPA) double mutation were analyzed for cytogenetically normal (CN)-AML. The KIT mutation was analyzed for core-binding factor AML. RESULTS: Within the cytogenetically favorable prognosis group, WT1 expression in AML with inv(16) or t(15;17) was significantly greater than that in AML with t(8;21). In cases with CN-AML, FLT3-ITD and NPM1 mutations both correlated with greater expression of WT1, and the CEBPA double mutation was related to lower WT1 expression. The existence of both FLT3-ITD and NPM1 mutations showed synergistically greater expression of WT1 in CN-AML. SNP in the WT1 gene (rs16754) was significantly associated with lower expression of WT1. The WT1 levels were not prognostic factors in the total cohort or any cytogenetic group or stratified by SNP status. CONCLUSION: Because WT1 expression has correlated with known prognostic factors, the prognostic effect of WT1 levels could be misunderstood depending on the distribution of the collaborative mutations in each cohort. We have concluded that the prognostic significance of WT1 at the diagnosis of AML is weak compared with the other established prognostic factors.
  • Hematogones Predict Better Outcome in Allogeneic Hematopoietic Stem Cell Transplantation Irrespective of Graft Sources
    Takashi Ishio; Junichi Sugita; Takahiro Tateno; Daisuke Hidaka; Eiko Hayase; Souichi Shiratori; Kohei Okada; Hideki Goto; Masahiro Onozawa; Masao Nakagawa; Daigo Hashimoto; Kaoru Kahata; Katsuya Fujimoto; Tomoyuki Endo; Takeshi Kondo; Takanori Teshima
    Biology of Blood and Marrow Transplantation, 24, 10, 1990, 1996, Elsevier BV, Oct. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Benign precursors of B lymphocytes, termed hematogones, are observed in the regenerative state of hematopoiesis following chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated that expansion of hematogones correlates with better clinical outcomes after allo-HSCT. We retrospectively analyzed the association between hematogones and clinical outcomes in 309 consecutive patients who underwent allo-HSCT, which is the largest population-based cohort reported so far. The incidence of hematogones was significantly higher in complete remission (CR) patients at the time of transplantation than in non-CR patients, after myeloablative conditioning than after reduced-intensity conditioning, with tacrolimus-based graft-versus-host disease (GVHD) prophylaxis than with cyclosporine-based prophylaxis, and with disease other than malignant lymphoma (all P < .05). Patients with hematogones developed less acute GVHD and infections than did those without them (P < .05). Emergence of hematogones was associated with superior GVHD-free relapse-free survival and lower nonrelapse mortality, and was an independent prognostic factor for overall survival, irrespective of donor sources.
  • 成人急性リンパ性白血病におけるIKZF1欠失およびCRLF2発現の解析(Analysis of IKZF1 deletion and CRLF2 expression in adult patients with acute lymphoblastic leukemia)
    橋口 淳一; 小野澤 真弘; 藤澤 真一; 高橋 秀一郎; 宮下 直洋; 早瀬 英子; 白鳥 聡一; 後藤 秀樹; 杉田 純一; 中川 雅夫; 橋本 大吾; 加畑 馨; 遠藤 知之; 山本 聡; 堤 豊; 長谷山 美仁; 永嶋 貴博; 盛 暁生; 太田 秀一; 宮城島 拓人; 柿木 康孝; 黒澤 光俊; 岩崎 博; 近藤 健; 豊嶋 崇徳
    臨床血液, 59, 9, 1648, 1648, (一社)日本血液学会-東京事務局, Sep. 2018
    English
  • The association between the incidence of intestinal graft-vs-host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation.
    Hidaka D; Hayase E; Shiratori S; Hasegawa Y; Ishio T; Tateno T; Okada K; Goto H; Sugita J; Onozawa M; Nakagawa M; Kahata K; Endo T; Hashimoto D; Teshima T
    Clinical transplantation, 32, 9, e13361, Sep. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Intestinal microbiota plays an important role in the regulation of allogeneic immune reaction after allogeneic hematopoietic stem cell transplantation (allo-SCT). Intestinal graft-vs-host disease (GVHD) is one of the major causes of mortality after allo-SCT and often complicated with intestinal dysbiosis. Recent studies suggest that antibiotic-induced dysbiosis is a risk factor for intestinal GVHD. We retrospectively evaluated the impacts of antibiotic use on the incidence of intestinal GVHD occurring before day 100 after allo-SCT. Among 213 patients who underwent allo-SCT, 200 patients achieving engraftment were analyzed. Antibiotics were classified into carbapenem, quinolone, penicillin, cephem, and glycopeptide. Among 128 patients who developed acute GVHD, intestinal GVHD developed in 36 patients. Patients with intestinal GVHD received significantly longer administration of carbapenem and glycopeptide compared to those without it in periengraftment period. In multivariate analysis, use of carbapenem for greater than 7 days was associated with an increased risk of intestinal GVHD. However, use of antibiotics for greater than 7 days was not associated with poor overall survival and high nonrelapse mortality. Long use of carbapenem in periengraftment period may be a risk for intestinal GVHD. Prospective studies are required to validate our findings.
  • Targeting the HTLV-I-Regulated BATF3/IRF4 Transcriptional Network in Adult T Cell Leukemia/Lymphoma
    Masao Nakagawa; Arthur L. Shaffer; Michele Ceribelli; Meili Zhang; George Wright; Da Wei Huang; Wenming Xiao; John Powell; Michael N. Petrus; Yibin Yang; James D. Phelan; Holger Kohlhammer; Sigrid P. Dubois; Hee Min Yoo; Emmanuel Bachy; Daniel E. Webster; Yandan Yang; Weihong Xu; Xin Yu; Hong Zhao; Bonita R. Bryant; Joji Shimono; Takashi Ishio; Michiyuki Maeda; Patrick L. Green; Thomas A. Waldmann; Louis M. Staudt
    Cancer Cell, 34, 2, 286, 297.e10, Elsevier BV, Aug. 2018, [Peer-reviewed], [Lead author]
    Scientific journal
  • A multiprotein supercomplex controlling oncogenic signalling in lymphoma
    James D. Phelan; Ryan M. Young; Daniel E. Webster; Sandrine Roulland; George W. Wright; Monica Kasbekar; Arthur L. Shaffer; Michele Ceribelli; James Q. Wang; Roland Schmitz; Masao Nakagawa; Emmanuel Bachy; Da Wei Huang; Yanlong Ji; Lu Chen; Yandan Yang; Hong Zhao; Xin Yu; Weihong Xu; Maryknoll M. Palisoc; Racquel R. Valadez; Theresa Davies-Hill; Wyndham H. Wilson; Wing C. Chan; Elaine S. Jaffe; Randy D. Gascoyne; Elias Campo; Andreas Rosenwald; German Ott; Jan Delabie; Lisa M. Rimsza; Fausto J. Rodriguez; Fayez Estephan; Matthias Holdhoff; Michael J. Kruhlak; Stephen M. Hewitt; Craig J. Thomas; Stefania Pittaluga; Thomas Oellerich; Louis M. Staudt
    Nature, 560, 7718, 387, 391, Springer Science and Business Media LLC, Aug. 2018, [Peer-reviewed]
    Scientific journal
  • Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia
    Junichi Hashiguchi; Masahiro Onozawa; Satoshi Oguri; Shinichi Fujisawa; Masahisa Tsuji; Kohei Okada; Masao Nakagawa; Daigo Hashimoto; Kaoru Kahata; Takeshi Kondo; Chikara Shimizu; Takanori Teshima
    Journal of Molecular Diagnostics, 20, 4, 446, 454, Elsevier B.V., 01 Jul. 2018, [Peer-reviewed]
    English, Scientific journal
  • AMLにおけるWT1発現量と染色体・遺伝子異常の関連
    日高 大輔; 小野澤 真弘; 橋口 淳一; 宮下 直洋; 笠原 耕平; 藤澤 真一; 早瀬 英子; 岡田 耕平; 白鳥 聡一; 後藤 秀樹; 杉田 純一; 中川 雅夫; 加畑 馨; 橋本 大吾; 遠藤 知之; 山本 聡; 堤 豊; 長谷山 美仁; 永嶋 貴博; 盛 暁生; 太田 秀一; 酒井 基; 石原 敏道; 今井 陽俊; 宮城島 拓人; 柿木 康孝; 黒澤 光俊; 小林 一; 岩崎 博; 清水 力; 近藤 健; 豊嶋 崇徳
    臨床血液, 59, 7, 964, 964, (一社)日本血液学会-東京事務局, Jul. 2018
    Japanese
  • A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction.
    Naohiro Miyashita; Masahiro Onozawa; Koji Hayasaka; Takahiro Yamada; Ohsuke Migita; Kenichiro Hata; Kohei Okada; Hideki Goto; Masao Nakagawa; Daigo Hashimoto; Kaoru Kahata; Takeshi Kondo; Shinji Kunishima; Takanori Teshima
    Annals of hematology, 97, 4, 629, 640, Apr. 2018, [International Magazine]
    English, Scientific journal, We identified a novel heterozygous ITGB3 p.T720del mutation in a pedigree with macrothrombocytopenia exhibiting aggregation dysfunction. Platelet aggregation induced by ADP and collagen was significantly reduced, while ristocetin aggregation was normal. Integrin αIIbβ3 was partially activated in a resting status, but platelet expression of αIIbβ3 was downregulated. Functional analysis using a cell line showed spontaneous phosphorylation of FAK in αIIb/β3 (p.T720del)-transfected 293T cells in suspension conditions. Abnormal cytoplasmic protrusions, membrane ruffling, and cytoplasmic localization of αIIbβ3 were observed in αIIb/β3 (p.T720del)-transfected CHO cells. Such morphological changes were reversed by treatment with an FAK inhibitor. These findings imply spontaneous, but partial, activation of αIIbβ3 followed by phosphorylation of FAK as the initial mechanism of abnormal thrombopoiesis. Internalization and decreased surface expression of αIIbβ3 would contribute to aggregation dysfunction. We reviewed the literature of congenital macrothrombocytopenia associated with heterozygous ITGA2B or ITGB3 mutations. Reported mutations were highly clustered at the membrane proximal region of αIIbβ3, which affected the critical interaction between αIIb R995 and β3 D723, resulting in a constitutionally active form of the αIIbβ3 complex. Macrothrombocytopenia caused by a heterozygous activating mutation of ITGA2B or ITGB3 at the membrane proximal region forms a distinct entity of rare congenital thrombocytopenia.
  • T-cell depletion effects of low-dose antithymocyte globulin for GVHD prophylaxis in HLA-matched allogeneic peripheral blood stem cell transplantation.
    Souichi Shiratori; Mizuha Kosugi-Kanaya; Eiko Hayase; Kohei Okada; Hideki Goto; Junichi Sugita; Masahiro Onozawa; Masao Nakagawa; Kaoru Kahata; Daigo Hashimoto; Tomoyuki Endo; Takeshi Kondo; Takanori Teshima
    Transplant immunology, 46, 21, 22, Feb. 2018, [International Magazine]
    English
  • Chimeric antigen receptor modified T cells that target chemokine receptor CCR4 as a therapeutic modality for T-cell malignancies
    Liyanage P. Perera; Meili Zhang; Masao Nakagawa; Michael N. Petrus; Michiyuki Maeda; Marshall E. Kadin; Thomas A. Waldmann; Pin-Yu Perera
    AMERICAN JOURNAL OF HEMATOLOGY, 92, 9, 892, 901, Sep. 2017, [Peer-reviewed]
    English, Scientific journal
  • Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images
    Takahiro Tateno; Masahiro Onozawa; Junichi Hashiguchi; Takashi Ishio; Sayaka Yuzawa; Satomi Matsuoka; Mizuha Kosugi-Kanaya; Kohei Okada; Souichi Shiratori; Hideki Goto; Taichi Kimura; Junichi Sugita; Masao Nakagawa; Daigo Hashimoto; Kaoru Kahata; Katsuya Fujimoto; Tomoyuki Endo; Takeshi Kondo; Shinya Tanaka; Satoshi Hashino; Takanori Teshima
    TRANSPLANT INFECTIOUS DISEASE, 19, 4, Aug. 2017, [Peer-reviewed]
    English, Scientific journal
  • Cytokine receptor signaling is required for the survival of ALK- anaplastic large cell lymphoma, even in the presence of JAK1/STAT3 mutations
    Jing Chen; Yong Zhang; Michael N. Petrus; Wenming Xiao; Alina Nicolae; Mark Raffeld; Stefania Pittaluga; Richard N. Bamford; Masao Nakagawa; Sunny Tianyi Ouyang; Alan L. Epstein; Marshall E. Kadin; Annarose Del Mistro; Richard Woessner; Elaine S. Jaffe; Thomas A. Waldmann
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114, 15, 3975, 3980, Apr. 2017, [Peer-reviewed]
    English, Scientific journal
  • Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2
    Daniel J. Hodson; Arthur L. Shaffer; Wenming Xiao; George W. Wright; Roland Schmitz; James D. Phelan; Yandan Yang; Daniel E. Webster; Lixin Rui; Holger Kohlhammer; Masao Nakagawa; Thomas A. Waldmann; Louis M. Staudt
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113, 14, E2039, E2046, Apr. 2016, [Peer-reviewed]
    English, Scientific journal
  • Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma
    Yibin Yang; Priscilla Kelly; Arthur L. Shaffer; Roland Schmitz; Hee Min Yoo; Xinyue Liu; Da Wei Huang; Daniel Webster; Ryan M. Young; Masao Nakagawa; Michele Ceribelli; George W. Wright; Yandan Yang; Hong Zhao; Xin Yu; Weihong Xu; Wing C. Chan; Elaine S. Jaffe; Randy D. Gascoyne; Elias Campo; Andreas Rosenwald; German Ott; Jan Delabie; Lisa Rimsza; Louis M. Staudt
    CANCER CELL, 29, 4, 494, 507, Apr. 2016, [Peer-reviewed]
    English, Scientific journal
  • Gain-of-function CCR4 mutations in adult T cell leukemia/lymphoma
    Masao Nakagawa; Roland Schmitz; Wenming Xiao; Carolyn K. Goldman; Weihong Xu; Yandan Yang; Xin Yu; Thomas A. Waldmann; Louis M. Staudt
    JOURNAL OF EXPERIMENTAL MEDICINE, 211, 13, 2497, 2505, Dec. 2014, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis
    Miyuki Suguro; Noriaki Yoshida; Akira Umino; Harumi Kato; Hiroyuki Tagawa; Masao Nakagawa; Noriko Fukuhara; Sivasundaram Karnan; Ichiro Takeuchi; Toby D. Hocking; Kotaro Arita; Kennosuke Karube; Shinobu Tsuzuki; Shigeo Nakamura; Tomohiro Kinoshita; Masao Seto
    CANCER SCIENCE, 105, 7, 897, 904, Jul. 2014, [Peer-reviewed]
    English, Scientific journal
  • Clinical impact of cycling the administration of antibiotics for febrile neutropenia in Japanese patients with hematological malignancy
    S. Hashino; L. Morita; H. Kanamori; M. Takahata; M. Onozawa; M. Nakagawa; T. Kawamura; F. Fujisawa; K. Kahata; K. Izumiyama; M. Yonezumi; K. Chiba; T. Kondo; M. Asaka
    EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES, 31, 2, 173, 178, Feb. 2012, [Peer-reviewed]
    English, Scientific journal
  • Synergistic effect of Bcl2, Myc and Ccnd1 transforms mouse primary B cells into malignant cells
    Masao Nakagawa; Shinobu Tsuzuki; Keiichiro Honma; Osamu Taguchi; Masao Seto
    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 96, 9, 1318, 1326, Sep. 2011, [Peer-reviewed]
    English, Scientific journal
  • Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses
    Kennosuke Karube; Masao Nakagawa; Shinobu Tsuzuki; Ichiro Takeuchi; Keiichiro Honma; Yasuhiro Nakashima; Norio Shimizu; Young-Hyeh Ko; Yasuo Morishima; Koichi Ohshima; Shigeo Nakamura; Masao Seto
    BLOOD, 118, 12, 3195, 3204, Sep. 2011, [Peer-reviewed]
    English, Scientific journal
  • Clonal evolution of adult T-cell leukemia/lymphoma takes place in the lymph nodes
    Akira Umino; Masao Nakagawa; Atae Utsunomiya; Kunihiro Tsukasaki; Naoya Taira; Naoyuki Katayama; Masao Seto
    BLOOD, 117, 20, 5473, 5478, May 2011, [Peer-reviewed]
    English, Scientific journal
  • Diversity of genome profiles in malignant lymphoma
    Masao Seto; Keiichiro Honma; Masao Nakagawa
    CANCER SCIENCE, 101, 3, 573, 578, Mar. 2010, [Peer-reviewed]
    English
  • TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas
    Keiichiro Honma; Shinobu Tsuzuki; Masao Nakagawa; Hiroyuki Tagawa; Shigeo Nakamura; Yasuo Morishima; Masao Seto
    BLOOD, 114, 12, 2467, 2475, Sep. 2009, [Peer-reviewed]
    English, Scientific journal
  • Metric learning for DNA microarray data analysis
    Ichiro Takeuchi; Masao Nakagawa; Masao Seto
    INTERNATIONAL WORKSHOP ON STATISTICAL-MECHANICAL INFORMATICS 2009 (IW-SMI 2009), 197, 2009, [Peer-reviewed]
    English, International conference proceedings
  • Array CGH analysis of PTCL-U reveals a distinct subgroup with genetic alterations similar to lymphoma-type ATLL.
    Nakagawa M; Nakagawa-Oshiro A; Karnan S; Tagawa H; Utsunomiya A; Nakamura S; Takeuchi I; Ohshima K; Seto M
    Clin Cancer Res, 15, 1, 30, 38, Jan. 2009, [Peer-reviewed]
    English, Scientific journal, PURPOSE:Peripheral T-cell lymphoma, unspecified (PTCL-U) comprises histopathologically and clinically heterogeneous groups. The purpose of this study was to identify subgroups with distinct genetic, histopathologic, and prognostic features.

    EXPERIMENTAL DESIGN:

    We used array comparative genomic hybridization (CGH) for high-resolution analysis of 51 PTCL-U patients and the array data for examining possible correlations of histopathologic and clinical features. Moreover, we compared the genetic, histopathologic, and prognostic features of the PTCL-U cases with those of 59 cases of lymphoma-type adult T-cell leukemia/lymphoma (ATLL).

    RESULTS:We identified 32 regions with frequent genomic imbalance, 1 region with high copy number gain at 14q32.2, and 1 region with homozygous loss at 9p21.3. Gains of 7p and 7q and loss of 9p21.3 showed a significant association with poor prognosis. PTCL-U cases with genomic imbalance showed distinct histopathologic and prognostic features compared with such cases without alteration and a marked genetic, histopathologic, and prognostic resemblance to lymphoma-type ATLL.

    CONCLUSIONS:The array CGH enabled us to identify the frequently altered genomic regions with strong prognostic power among PTCL-U cases. A correlative analysis using the array CGH data disclosed a subgroup in PTCL-U with genomic alterations and with histopathologic and clinical relevance. In addition to histopathologic similarity, the strong genetic and prognostic resemblance between PTCL-U cases with genomic imbalance detected by array CGH and lymphoma-type ATLL seems to support the notion that the former may constitute a distinct PTCL-U subgroup.
  • The potential of copy number gains and losses, detected by array-based comparative genomic hybridization, for computational differential diagnosis of B-cell lymphomas and genetic regions involved in lymphomagenesis
    Ichiro Takeuchi; Hiroyuki Tagawa; Akira Tsujikawa; Masao Nakagawa; Miyuki Katayama-Suguro; Ying Guo; Masao Seto
    Haematologica-The Hematology Journal, 94, 1, 61, 69, Jan. 2009, [Peer-reviewed]
    English, Scientific journal
  • Array Comparative Genomic Hybridization Analysis of PTCL-U Reveals a Distinct Subgroup with Genetic Alterations Similar to Lymphoma-Type Adult T-Cell Leukemia/Lymphoma
    Masao Nakagawa; Aya Nakagawa-Oshiro; Sivasundaram Karnan; Hiroyuki Tagawa; Atae Utsunomiya; Shigeo Nakamura; Ichiro Takeuchi; Koichi Ohshima; Masao Seto
    CLINICAL CANCER RESEARCH, 15, 1, 30, 38, Jan. 2009, [Peer-reviewed]
    English, Scientific journal
  • Graft-versus-tumor effect after reduced-intensity allogeneic hematopoietic stem cell transplantation in a patient with advanced colon cancer
    Satoshi Hashino; Sumiko Kobayashi; Mutsumi Takahata; Masahiro Onozawa; Masao Nakagawa; Takahito Kawamura; Fumie Fujisawa; Koh Izumiyama; Kaoru Kahata; Takeshi Kondo; Masahiro Asaka
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 13, 2, 176, 180, Apr. 2008, [Peer-reviewed]
    English, Scientific journal
  • [Array comparative genomic hybridilyzation analysis for unclassified peripheral T-cell lymphoma revealed possible subgrouping].
    Nakagawa M
    [Rinsho ketsueki] The Japanese journal of clinical hematology, 49, 3, 165, 170, The Japanese Society of Hematology, Mar. 2008, [Peer-reviewed]
    Japanese
  • Administration of micafungin as prophylactic antifungal therapy in patients undergoing allogeneic stem cell transplantation.
    Hashino S; Morita L; Takahata M; Onozawa M; Nakagawa M; Kawamura T; Fujisawa F; Kahata K; Izumiyama K; Yonezumi M; Chiba K; Kondo T; Asaka M
    International journal of hematology, 87, 1, 91, 97, 1, Jan. 2008, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Invasive fungal infection is one of the major causes of death in neutropenic patients undergoing allogeneic stem cell transplantation (SCT). Although prophylactic antifungal therapy with fluconazole (FLCZ) has become the standard care for these patients, there remains a need for more effective and cost-beneficial alternative drugs. We conducted a prospective study to evaluate the usefulness of the administration of micafungin (MCFG) as a prophylactic antifungal therapy for patients undergoing allogeneic SCT. The results were compared with previous data for patients who had received FLCZ. A total of 44 patients who underwent allogeneic SCT were enrolled in the study. Data from 29 patients who received allogeneic SCT using prophylactic FLCZ before this study were used as historical control data. Underlying diseases included acute leukemia (n = 16), non-Hodgkin's lymphoma (n = 11), myelodysplastic syndrome (n = 6), and others (n = 11) in the MCFG group and acute leukemia (n = 18), chronic myelogenous leukemia (n = 6), and others (n = 5) in the FLCZ group. The median durations of administration of MCFG and FLCZ were 36 and 34 days, respectively. Prophylactic success, defined as the absence of proven, probable, and possible invasive fungal infection (IFI) until the end of prophylactic therapy was achieved in 36 (87.8%) of the 41 evaluated patients in the MCFG group and in 65.5% of the patients in the FLCZ group (P = 0.038). No patients in the MCFG group showed proven or probable IFI, whereas proven or probable IFI was observed in three patients in the FLCZ group. Four patients in the MCFG group required dose escalation due to febrile neutropenia. Although one patient in the MCFG group required the discontinuation of MCFG due to allergic skin eruption (grade 2), none of the other patients in either group required dose reduction due to adverse effects. Although the study design was not a prospective randomized trial, our results indicate that the administration of MCFG at a daily dose of 100 mg is promising for prophylactic antifungal therapy in patients undergoing allogeneic SCT.
  • TNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphoma
    Keiichiro Honma; Shinobu Tsuzuki; Masao Nakagawa; Sivasundaram Karnan; Yoshifusa Aizawa; Won Seog Kim; Yoon-Duk Kim; Young-Hyeh Ko; Masao Seto
    GENES CHROMOSOMES & CANCER, 47, 1, 1, 7, Jan. 2008, [Peer-reviewed]
    English, Scientific journal
  • Chromosomal imbalances are associated with outcome of Helicobacter pylori eradication in t(11;18)(q21;q21) negative gastric mucosa-associated lymphoid tissue lymphomas
    Noriko Fukuhara; Tsuneya Nakamura; Masao Nakagawa; Hiroyuki Tagawa; Ichiro Takeuchi; Yasushi Yatabe; Yasuo Morishima; Shigeo Nakamura; Masao Seto
    GENES CHROMOSOMES & CANCER, 46, 8, 784, 790, Aug. 2007, [Peer-reviewed]
    English, Scientific journal
  • Successful reduced-intensity stem cell transplantation with cord blood for a poor-prognosis adult with refractory chronic active Epstein-Barr virus infection
    Masao Nakagawa; Satoshi Hashino; Mutsumi Takahata; Takahito Kawamura; Fumie Fujisawa; Kaoru Kahata; Takeshi Kondo; Masahiro Imamura; Sachiko Ando; Masahiro Asaka
    INTERNATIONAL JOURNAL OF HEMATOLOGY, 85, 5, 443, 445, Jun. 2007, [Peer-reviewed]
    English, Scientific journal
  • Relationship between preexisting anti-varicella-zoster virus (VZV) antibody and clinical VZV reactivation in hematopoietic stem cell transplantation recipients
    Masahiro Onozawa; Satoshi Hashino; Mutsumi Takahata; Fumie Fujisawa; Takahito Kawamura; Masao Nakagawa; Kaoru Kahata; Takeshi Kondo; Shuichi Ota; Junji Tanaka; Masahiro Imamura; Masahiro Asaka
    JOURNAL OF CLINICAL MICROBIOLOGY, 44, 12, 4441, 4443, Dec. 2006, [Peer-reviewed]
    English, Scientific journal
  • MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10
    M Nakagawa; Y Hosokawa; M Yonezumi; K Izumiyama; R Suzuki; S Tsuzuki; M Asaka; M Seto
    BLOOD, 106, 13, 4210, 4216, Dec. 2005, [Peer-reviewed]
    English, Scientific journal
  • AP12-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-kappa B binding elements: Evidence for a positive feed-back loop pathway resulting in unremitting NF-kappa B activation
    Y Hosokawa; H Suzuki; M Nakagawa; TH Lee; M Seto
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 334, 1, 51, 60, Aug. 2005, [Peer-reviewed]
    English, Scientific journal
  • Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18) (q21;q21) MALT lymphoma
    K Izumiyama; M Nakagawa; M Yonezumi; Y Kasugai; R Suzuki; H Suzuki; S Tsuzuki; Y Hosokawa; M Asaka; M Seto
    ONCOGENE, 22, 50, 8085, 8092, Nov. 2003, [Peer-reviewed]
    English, Scientific journal
■ Other Activities and Achievements
■ Syllabus
  • 医学総論, 2024年, 博士後期課程, 医学研究科
  • 基本医学研究, 2024年, 修士課程, 医学院
  • 基本医学総論, 2024年, 修士課程, 医学院
  • 医学総論, 2024年, 博士後期課程, 医学院
  • 医学総論, 2024年, 博士後期課程, 医学院
  • 基盤医学研究, 2024年, 博士後期課程, 医学院
  • 臨床医学研究, 2024年, 博士後期課程, 医学院
  • 統合・血液学, 2024年, 学士課程, 医学部
■ Research Themes
  • CRISPR screening for functional gene discovery in NK cells
    Grants-in-Aid for Scientific Research
    01 Apr. 2024 - 31 Mar. 2027
    中川 雅夫
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 24K02315
  • Investigation of molecular mechanisms for constitutive IRF4 expression in T-cell malignancies
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2021 - 31 Mar. 2024
    中川 雅夫
    目的１）成人T細胞性白血病リンパ腫におけるIRF4の恒常的高発現が維持される分子メカニズムの解明とその制御方法の開発
    ・ CRISPRゲノムワイド遺伝子ノックアウトによるIRF4蛋白発現スクリーニング： 成人T細胞性白血病リンパ腫患者由来細胞株に対して19,114遺伝子を標的としたsgRNAライブラリーをレンチウイルスで感染させ、フローサイトメーターでIRF4低発現分画をソートする。ソート前と比較してソート後に増加した細胞でノックアウトされていた遺伝子を同定する計画で、この予備実験を終えた。
    ・ 化合物ライブラリーによるIRF4蛋白発現スクリーニング: IRF4発現変化の検出系として、フローサイトメーターを用いたHigh throughput screening (HTS)の系を確立した。北大化合物ライブラリー（約3000個の既存薬を搭載）の中から、成人T細胞性白血病リンパ腫患者由来細胞株のIRF4発現低下をもたらす候補化合物を同定した。
    ・ 機能的エンハンサー解析:成人T細胞性白血病リンパ腫細胞株と臨床検体のATACseqからIRF4遺伝子座周辺のopen chromatin領域の解析を進めた。
    目的２）T細胞性腫瘍全体におけるIRF4恒常的発現異常の分布と頻度
    ・ 組織マイクロアレイ作成：北日本血液研究会(http://www.njhsg.com)と連携し、T細胞性腫瘍の組織マイクロアレイを作成した。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 21H02775
  • Identification of novel inhibitors for essential genes in cell proliferation and survival in T-cell lymphomas
    Division of Strategic Planning and Evaluation (The iD3 Booster)
    Oct. 2021 - Sep. 2023
    Masao Nakagawa
    AMED, 北海道大学大学院医学研究院, Principal investigator
  • CRISPR screening for identification of molecular targets of T/NK cell lymphomas
    Grants-in-Aid for Scientific Research
    01 Apr. 2018 - 31 Mar. 2021
    Nakagawa Masao
    In this study, we performed genome-wide CRISPR-Cas9 screens in multiple T/NK lymphoma cell lines for identifying essential genes for cellular proliferation/survival in a series of T/NK cell lymphoma cell lines. Positive and negative control sgRNAs were correctly identified through the entire screening, confirming the validity of the screening results. We identified genes which were selectively essential for each diease group in T/NK cell lymphomas. Some among the essential genes were confirmed in the follow-up functional experiments. All together, we established an entire list of candidate genes for molecular targeted therapies in T/NK cell lymphomas.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 18K08313
  • Grant-in-Aid for Scientific Research (C), Research Project Number:18K08313
    2018 - 2020
    Masao Nakagawa
    JSPS, Principal investigator, Competitive research funding
  • Identification of molecular biomarkers for chemotherapy in T-cell lymphomas
    研究助成金
    2019
    Masao Nakagawa
    Research Grant from Astellas Foundation for Research on Metabolic Disorders, Principal investigator
  • Research Grant from Suhara Memorial Foundation
    2018
    Masao Nakagawa
    Principal investigator, Competitive research funding
  • Project of Translational and Clinical Research Core Centers, Translational Research Network Program.
    2018
    Masao Nakagawa
    AMED, Principal investigator, Competitive research funding
  • Project of Translational and Clinical Research Core Centers, Translational Research Network Program.
    2017
    Masao Nakagawa
    AMED, Principal investigator, Competitive research funding
  • Research Grant from Takada Research Foundation.
    2017
    Masao Nakagawa
    Principal investigator, Competitive research funding
  • Research Grant from SENSHIN Medical Research Foundation.
    2017
    Masao Nakagawa
    Principal investigator, Competitive research funding
  • 新規スクリーニング法を用いた機能的T細胞リンパ腫がん遺伝子の網羅的探索
    科学研究費助成事業
    2011 - 2011
    中川 雅夫
    ATLL(成人T細胞性リンパ腫白血病)リンパ腫型は、日本で最も多いT細胞性リンパ腫である。HTLV-1ウイルスの感染がその成立の前提条件ではあるが、それだけでは腫瘍化せず、何らかの付加的遺伝子異常が必須と考えられる。しかしながら、リンパ腫の病態形成に必須の遺伝子は未知である。
    本研究はT細胞性リンパ腫形成に働く遺伝子を、機能的スクリーニングにより網羅的に検索することを目的とする。具体的には、ATLLリンパ腫型細胞株からレトロウイルスcDNAライブラリーを作製し、正常のT細胞にライブラリーを導入し、形質転換能、マウスへの移植による造腫瘍能を指標に、リンパ腫形成に必須の遺伝子を探索するものである。
    本年度は、その手法を確立するために以下の研究を行い、一定の成果を収めた。
    (1)マウスの胎児肝細胞から造血細胞を純化し、OP9-DL1ストローマ細胞と共培養することにより、T細胞をin vitroで分化・増殖させることに成功した。
    (2)次に、この共培養のシステムにおいて、レトロウイルスを感染させることにより、T細胞に遺伝子を導入することに成功した。T細胞はCD3陰性からCD4陽性CD8陽性、さらにはCD4単独陽性と各分化段階の細胞が見られ、T細胞性リンパ腫の発生段階に対応する任意の細胞に遺伝子を発現させることが可能であった。
    (3)そこで、この共培養を応用したレトロウイルスによるT細胞への遺伝子導入システムが、T細胞性リンパ腫の発がん研究に応用できるかどうかを、モデル系で検討した。この目的のために、T細胞に活性型RasやAkt,Myc,ERGなどの既知のがん原性遺伝子を導入し、T細胞の増殖動態を観察した。その結果、いずれの場合もT細胞の増殖が確認でき、特にRas,Mycで強い作用を観察した。
    以上から、共培養を応用した本システムがT細胞性リンパ腫研究に応用可能であることが明らかとなった。
    日本学術振興会, 若手研究(B), 愛知県がんセンター(研究所), 23791095
  • Grant-in-Aid for Young Scientists (B), Research Project Number:23791095
    2011
    Masao Nakagawa
    JSPS, Principal investigator, Competitive research funding
  • Identification of molecular basis of acute-and lymphoma-type adult T-cell leukemia/lymphoma
    Grants-in-Aid for Scientific Research
    2009 - 2010
    NAKAGAWA Masao
    Acute-type adult T-cell leukemia/lymphoma (ATLL) cases frequently have lymph node lesions. I performed detailed genomic analysis and clarified; 1) a part of such cases had genomic alterations similar to those frequently found in lymphoma-type ATLL, 2) multiple subclones with various additional genomic alterations were frequently found in a lymph node of individual cases and a selected subclone among the lymph node subclones appeared in peripheral blood. These new findings indicate that a part of acute-type ATLL cases should be categorized as lymphoma-type ATLL with leukemic change.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Aichi Cancer Center Research Institute, 21790930
  • Grant-in-Aid for Young Scientists (B), Research Project Number:21790930
    2009 - 2010
    Masao Nakagawa
    JSPS, Principal investigator, Competitive research funding
  • Array CGH analytics and gene expression analytics revealed distinct subgroups in Peripheral T cell lymphomas
    Grants-in-Aid for Scientific Research
    2007 - 2008
    NAKAGAWA Masao
    末梢性T細胞リンパ腫(PTCL)の中で、明確な疾患名に診断できない症例は末梢性T細胞リンパ腫・分類不能型(PTCL-U)として扱われる。PTCL-Uは未知の疾患が混在していると考えられるが、明確な報告はなかった。本研究ではPTCL-U51症例にアレイCGH法によるゲノム異常解析を行い、ゲノム異常様式・予後・病理像すべてに相関する二つの疾患群に分類できることをはじめて明らかにした。また二つのうち片方の疾患群は、別のPTCLである成人T細胞性白血病リンパ腫・リンパ腫型とよく似た均質な一群であることも明らかにした。
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Aichi Cancer Center Research Institute, 19790678
  • Grant-in-Aid for Young Scientists (B), Research Project Number:19790678
    2007 - 2008
    Masao Nakagawa
    JSPS, Principal investigator, Competitive research funding