今月の研究者

山本 豪

山本 豪

1) キャリア
1997年に東京大学を卒業後、東京大学附属病院および東京厚生年金病院で臨床研修を行いました。1999年東京大学大学院に入学し、遺伝子ノックアウトマウスを用いた造血器腫瘍関連遺伝子の機能解析を中心とした研究を行いました。同大学院修了後は、東京大学医学部附属病院の血液・腫瘍内科および輸血部で臨床に従事するとともに、マイクロアレイを用いた染色体コピー数異常の網羅的解析アルゴリズムの開発などの研究を行いました。2009年より、東京大学医学部附属病院血液・腫瘍内科助教として、特にリンパ腫、多発性骨髄腫の診療において中心的役割を担いました。2012年4月からは虎の門病院血液内科に赴任いたしました。

2) 研究分野
虎の門病院では、多発性骨髄腫、リンパ腫をはじめとする各種造血器疾患の診療を行うとともに、臨床研究を進めています。当院では難治性疾患に対して、造血幹細胞移植(自家移植、同種移植)を数多く行っており、移植に関する臨床研究も行っています。また、造血器疾患は比較的まれな疾患も多く、他施設と協力して、多施設共同研究を行っています。特に多発性骨髄腫については、当院が中心となり臨床研究を実施しています。

3) 今後の抱負・アピール
造血器疾患では、近年、新規薬剤の開発が進み、治療成績が向上しています。しかし、まだその成績は決して満足できるものではなく、日々の臨床における、疑問点や問題点を少しでも解決できるよう臨床研究を進めていきたいと思います。

発表・論文

4) 文献

1: Miyazaki K, Asano N, Yamada T, Miyawaki K, Sakai R, Igarashi T, Nishikori M, Ohata K, Sunami K, Yoshida I, Yamamoto G, Takahashi N, Okamoto M, Yano H, Nishimura Y, Tamaru S, Nishikawa M, Izutsu K, Kinoshita T, Suzumiya J, Ohshima K, Kato K, Katayama N, Yamaguchi M; CD5+ DLBCL Treatment Study Group. DA-EPOCH-R combined with high-dose methotrexate in patients with newly diagnosed stage II-IV CD5-positive diffuse large B-cell lymphoma: a single-arm, open-label, phase 2 study. Haematologica. 2019 Oct 24. pii: haematol.2019.231076.

2: Fukuhara N, Yamamoto G, Tsujimura H, Chou T, Shibayama H, Yanai T, Shibuya K, Izutsu K. Retreatment with brentuximab vedotin in patients with relapsed/refractory classical Hodgkin lymphoma or systemic anaplastic large-cell lymphoma: a multicenter retrospective study. Leuk Lymphoma. 2019 Aug 22:1-5.

3: Wada S, Asano-Mori Y, Yamamoto H, Yuasa M, Kageyama K, Kaji D, Nishida A, Ishiwata K, Takagi S, Yamamoto G, Uchida N, Yoneyama A, Makino S, Taniguchi S. No post-transplant pure red cell aplasia development in 106 major ABO incompatible cord blood transplantation. Bone Marrow Transplant. 2019 May;54(5):765-768.

4: Mitsuki T, Kimura M, Araoka H, Kageyama K, Takagi S, Yamamoto G, Nakamura S, Miyazaki Y, Uchida N, Yoneyama A, Taniguchi S. Cryptococcal meningitis following umbilical cord blood transplantation, association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients. J Infect Chemother. 2019 Apr;25(4):289-292.

5: Imafuku A, Yamamoto G, Takemura K, Hasegawa E, Sawa N, Kawada M, Sekine A, Hoshino J, Takaichi K, Fujii T, Ohashi K, Ubara Y. Acute Kidney Injury by Renal Hemosiderosis Secondary to Primary Cold Agglutinin Disease Associated with an Excessive Alcohol Intake. Intern Med. 2018 Nov 15;57(22):3261-3265.

6: Kimura M, Araoka H, Yamamoto H, Nakamura S, Nagi M, Yamagoe S, Miyazaki Y, Ogura S, Mitsuki T, Yuasa M, Kaji D, Kageyama K, Nishida A, Taya Y, Shimazu H, Ishiwata K, Takagi S, Yamamoto G, Asano-Mori Y, Uchida N, Wake A, Taniguchi S, Yoneyama A. Micafungin Breakthrough Fungemia in Patients with Hematological Disorders. Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: e02183-17.

7: Suehara Y, Sakata-Yanagimoto M, Hattori K, Nanmoku T, Itoh T, Kaji D, Yamamoto G, Abe Y, Narita K, Takeuchi M, Matsue K, Sato T, Noguchi M, Baba N, Sakamoto T, Kusakabe M, Kurita N, Kato T, Yokoyama Y, Nishikii H, Obara N, Hasegawa Y, Chiba S. Liquid biopsy for the identification of intravascular large B-cell lymphoma. Haematologica. 2018 Jun;103(6):e241-e244.

8: Nakasone H, Terasako-Saito K, Hirano T, Wake A, Shimizu S, Kurita N, Yamazaki E, Usuki K, Akazawa K, Kanda J, Minauchi K, Yamamoto G, Tanimoto S, Kamoshita M, Yokoyama Y, Miyaoka E, Ota S, Kako S, Izutsu K, Kanda Y. Targeting complete response with upfront bortezomib consolidation versus observation after the achievement of complete response following autologous transplantation for multiple myeloma (TUBA study). Hematol Oncol. 2018 Feb;36(1):202-209.

9: Ota H, Yamamoto H, Kimura M, Araoka H, Fujii T, Umeyama T, Ohno H, Miyazaki Y, Kaji D, Taya Y, Nishida A, Ishiwata K, Tsuji M, Takagi S, Asano-Mori Y, Yamamoto G, Uchida N, Izutsu K, Masuoka K, Wake A, Yoneyama A, Makino S, Taniguchi S. Successful Treatment of Pulmonary Mucormycosis Caused by Cunninghamella bertholletiae with High-Dose Liposomal Amphotericin B (10 mg/kg/day) Followed by a Lobectomy in Cord Blood Transplant Recipients. Mycopathologia. 2017 Oct;182(9-10):847-853.

10: Kimura M, Araoka H, Yamamoto H, Asano-Mori Y, Nakamura S, Yamagoe S, Ohno H, Miyazaki Y, Abe M, Yuasa M, Kaji D, Kageyama K, Nishida A, Ishiwata K, Takagi S, Yamamoto G, Uchida N, Izutsu K, Wake A, Taniguchi S, Yoneyama A. Clinical and Microbiological Characteristics of Breakthrough Candidemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients in a Japanese Hospital. Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e01791-16.

11: Ogura M, Ishizawa K, Maruyama D, Uike N, Ando K, Izutsu K, Terui Y, Imaizumi Y, Tsukasaki K, Suzuki K, Izumi T, Usuki K, Kinoshita T, Taniwaki M, Uoshima N, Suzumiya J, Kurosawa M, Nagai H, Uchida T, Fukuhara N, Choi I, Ohmachi K, Yamamoto G, Tobinai K; Japanese Bendamustine Lymphoma Study Group. Bendamustine plus rituximab for previously untreated patients with indolent B-cell non-Hodgkin lymphoma or mantle cell lymphoma: a multicenter Phase II clinical trial in Japan. Int J Hematol. 2017 Apr;105(4):470-477.

12: Kimura M, Araoka H, Yoshida A, Yamamoto H, Abe M, Okamoto Y, Yuasa M, Kaji D, Kageyama K, Nishida A, Ishiwata K, Takagi S, Yamamoto G, Asano-Mori Y, Uchida N, Hishinuma A, Izutsu K, Wake A, Taniguchi S, Yoneyama A. Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital. BMC Infect Dis. 2016 Aug 5;16:372

13: Yamamoto H, Uchida N, Yuasa M, Kageyama K, Ota H, Kaji D, Nishida A, Ishiwata K, Takagi S, Tsuji M, Asano-Mori Y, Yamamoto G, Izutsu K, Masuoka K, Wake A, Yoneyama A, Makino S, Taniguchi S. A Novel Reduced-Toxicity Myeloablative Conditioning Regimen Using Full-Dose Busulfan, Fludarabine, and Melphalan for Single Cord Blood Transplantation Provides Durable Engraftment and Remission in Nonremission Myeloid Malignancies. Biol Blood Marrow Transplant. 2016 Oct;22(10):1844-1850.

14: Iriuchishima H, Ozaki S, Konishi J, Matsumoto M, Murayama K, Nakamura F, Yamamoto G, Handa H, Saitoh T, Nagura E, Shimizu K, Nojima Y, Murakami H. Primary Plasma Cell Leukemia in the Era of Novel Agents: A Multicenter Study of the Japanese Society of Myeloma. Acta Haematol. 2016;135(2):113-21.

15: Yamamoto H, Uchida N, Uchida Y, Nishida A, Ota H, Kageyama K, Nasu I, Wada S, Kaji D, Ishiwata K, Takagi S, Tsuji M, Asano-Mori Y, Matsuno N, Yamamoto G, Masuoka K, Izutsu K, Wake A, Yoneyama A, Makino S, Ito T, Hayashi M, Taniguchi S. Oral beclomethasone dipropionate as an initial treatment for stages 1-2 gastrointestinal tract acute graft-versus-host disease following unrelated cord blood transplantation. Ann Hematol. 2015 Dec;94(12):2073-5.

16: Watanabe M, Kaji D, Hashimoto-Maeda M, Yamamoto G, Asano-Mori Y, Uchida N, Taniguchi S, Izutsu K. [Subacute encephalopathy after high-dose methotrexate as prophylaxis for central nervous system relapse in a patient with intravascular large B-cell lymphoma]. Rinsho Ketsueki. 2015 Mar;56(3):329-34.

17: Kawamura K, Takamatsu H, Ikeda T, Komatsu T, Aotsuka N, Amano I, Yamamoto G, Watanabe K, Ohno Y, Matsue K, Kouzai Y, Tsukada N, Ishiyama K, Anzai N, Kato K, Suzuki R, Sunami K, Kanda Y. Cord Blood Transplantation for Multiple Myeloma: A Study from the Multiple Myeloma Working Group of the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2015 Jul;21(7):1291-8.

18: Yuasa M, Ishiwata K, Sugio T, Kaji D, Ota H, Tsuji M, Yamamoto H, Yamamoto G, Asano-Mori Y, Uchida N, Izutsu K, Taniguchi S. Herpes simplex virus type 2 fulminant hepatitis after umbilical cord blood transplantation for acute myeloid leukemia. Rinsho Ketsueki. 2014 Jun;55(6):682-6.

19: Yamamoto H, Uchida N, Matsuno N, Ota H, Kageyama K, Wada S, Kaji D, Nishida A, Ishiwata K, Takagi S, Tsuji M, Asano-Mori Y, Yamamoto G, Izutsu K, Masuoka K, Wake A, Yoneyama A, Makino S, Taniguchi S. Anti-HLA antibodies other than against HLA-A, -B, -DRB1 adversely affect engraftment and nonrelapse mortality in HLA-mismatched single cord blood transplantation: possible implications of unrecognized donor-specific antibodies. Biol Blood Marrow Transplant. 2014 Oct;20(10):1634-40.

20: Takagi S, Araoka H, Uchida N, Uchida Y, Kaji D, Ota H, Nishida A, Ishiwata K, Tsuji M, Yamamoto H, Ito T, Matsuno N, Yamamoto G, Asano-Mori Y, Hayashi M, Izutsu K, Masuoka K, Wake A, Makino S, Yoneyama A, Taniguchi S. A prospective feasibility study of primary prophylaxis against invasive fungal disease with voriconazole following umbilical cord blood transplantation with fludarabine-based conditioning. Int J Hematol. 2014;99(5):652-8.

21: Kobayashi T, Hangaishi A, Yamamoto G, Shinohara A, Morikawa T, Takazawa Y, Ota S, Imai Y, Nakamura F, Kurokawa M. Successful treatment of secondary NK/T-cell lymphoma of the testis. Ann Hematol. 2013 Jul;92(7):997-8.

22: Yoshimi A, Yamamoto G, Goto T, Koike K, Kurokawa M. Hepatocellular carcinoma in cirrhotic liver with graft-versus-host disease. Ann Hematol. 2012 Sep;91(9):1501-2.

23: Yamamoto G, Maki H, Ichikawa M, Kurokawa M. Pure red cell aplasia with follicular lymphoma showing regression and progression parallel to lymphoma. Int J Hematol. 2011 Dec;94(6):576-7.

24: Taoka K, Yamamoto G, Kaburaki T, Takahashi T, Araie M, Kurokawa M. Treatment of primary intraocular lymphoma with rituximab, high dose methotrexate, procarbazine, and vincristine chemotherapy, reduced whole-brain radiotherapy, and local ocular therapy. Br J Haematol. 2012 Apr;157(2):252-4.

25: Yamazaki S, Fujioka Y, Nakamura F, Ota S, Shinozaki A, Yamamoto G, Kamikubo Y, Nannya Y, Ichikawa M, Fukayama M, Kurokawa M. Composite diffuse large B-cell lymphoma and CD20-positive peripheral T-cell lymphoma. Pathol Int. 2011 Nov;61(11):662-6.

26: Suzuki R, Yamaguchi M, Izutsu K, Yamamoto G, Takada K, Harabuchi Y, Isobe Y, Gomyo H, Koike T, Okamoto M, Hyo R, Suzumiya J, Nakamura S, Kawa K, Oshimi K; NK-cell Tumor Study Group. Prospective measurement of Epstein-Barr virus-DNA in plasma and peripheral blood mononuclear cells of extranodal NK/T-cell lymphoma, nasal type. Blood. 2011 Dec 1;118(23):6018-22.

27: Toya T, Nishimoto N, Koya J, Nakagawa M, Nakamura F, Kandabashi K, Yamamoto G, Nannya Y, Ichikawa M, Kurokawa M. The first case of blastic plasmacytoid dendritic cell neoplasm with MLL-ENL rearrangement. Leuk Res. 2012 Jan;36(1):117-8.

28: Yoshiki Y, Yamamoto G, Takazawa Y, Nannya Y, Ishida J, Nagai R, Fukayama M, Kurokawa M. AL amyloidosis with severe gastrointestinal invasion and acute obstructive suppurative cholangitis. Ann Hematol. 2012 Mar;91(3):467-8.

29: Yamamoto G, Hosoi M, Miyagawa T, Ohmatsu H, Ichikawa M, Sugaya M, Kurokawa M. Evans syndrome with cytomegalovirus infection followed by emerging peripheral T-cell lymphoma. Ann Hematol. 2012 Jan;91(1):123-4.

30: Asano H, Imai Y, Ota S, Yamamoto G, Takahashi T, Fukayama M, Kurokawa M. CD30-positive anaplastic variant diffuse large B cell lymphoma: a rare case presented with cutaneous involvement. Int J Hematol. 2010 Oct;92(3):550-2.

31: Kobayashi CI, Yamamoto G, Hayashi A, Ota S, Imai Y, Fukayama M, Kurokawa M. Fatal amebic colitis after high-dose dexamethasone therapy for newly diagnosed multiple myeloma. Ann Hematol. 2011 Feb;90(2):225-6.

32: Asano H, Yamamoto G, Hosoi M, Takahashi T, Hangaishi A, Kurokawa M. Complete molecular remission in refractory acute myeloid leukemia with MLL/AF9 treated with gemtuzumab ozogamicin. Leuk Res. 2010 Jul;34(7):e152-3.

33: Takahashi T, Hangaishi A, Yamamoto G, Ichikawa M, Imai Y, Kurokawa M. HIV-negative, HHV-8-unrelated primary effusion lymphoma-like lymphoma: report of two cases. Am J Hematol. 2010 Jan;85(1):85-7.

34: Akagi T, Ito T, Kato M, Jin Z, Cheng Y, Kan T, Yamamoto G, Olaru A, Kawamata N, Boult J, Soukiasian HJ, Miller CW, Ogawa S, Meltzer SJ, Koeffler HP. Chromosomal abnormalities and novel disease-related regions in progression from Barrett's esophagus to esophageal adenocarcinoma. Int J Cancer. 2009 Nov 15;125(10):2349-59.

35: Hosoi M, Yamamoto G, Imai Y, Kurokawa M. Reversible posterior leukoencephalopathy syndrome following R-CHOP therapy for diffuse large B-cell lymphoma. Ann Hematol. 2010 Feb;89(2):207-8.

36: Lee SY, Kumano K, Nakazaki K, Sanada M, Matsumoto A, Yamamoto G, Nannya Y, Suzuki R, Ota S, Ota Y, Izutsu K, Sakata-Yanagimoto M, Hangaishi A, Yagita H, Fukayama M, Seto M, Kurokawa M, Ogawa S, Chiba S. Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma. Cancer Sci. 2009 May;100(5):920-6.

37: Yoshimi A, Nannya Y, Ueda K, Asano D, Yamamoto G, Kumano K, Hangaishi A, Matsui Y, Takahashi T, Imai Y, Sugawara Y, Kokudo N, Kurokawa M. Successful hematopoietic stem cell transplantation from an HLA-identical sibling in a patient with aplastic anemia after HLA-haploidentical living-related liver transplantation for fulminant hepatitis. Biol Blood Marrow Transplant. 2009 Mar;15(3):389-90.

38: Akagi T, Ogawa S, Dugas M, Kawamata N, Yamamoto G, Nannya Y, Sanada M, Miller CW, Yung A, Schnittger S, Haferlach T, Haferlach C, Koeffler HP. Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype. Haematologica. 2009 Feb;94(2):213-23.

39: Yoshimi M, Nannya Y, Watanabe T, Asai T, Ichikawa M, Yamamoto G, Kumano K, Hangaishi A, Imai Y, Takahashi T, Chiba S, Kurokawa M. Acute eosinophilic pneumonia is a non-infectious lung complication after allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2009 Mar;89(2):244-248.

40: Ueda K, Yamamoto G, Shinohara A, Hangaishi A, Kurokawa M. Early onset of acute lymphoblastic leukemia with MLL rearrangement after autologous stem cell transplantation for multiple myeloma. Ann Hematol. 2009 Aug;88(8):813-4.

41: Akagi T, Shih LY, Kato M, Kawamata N, Yamamoto G, Sanada M, Okamoto R, Miller CW, Liang DC, Ogawa S, Koeffler HP. Hidden abnormalities and novel classification of t(15;17) acute promyelocytic leukemia (APL) based on genomic alterations. Blood. 2009 Feb 19;113(8):1741-8.

42: Kawamata N, Ogawa S, Yamamoto G, Lehmann S, Levine RL, Pikman Y, Nannya Y, Sanada M, Miller CW, Gilliland DG, Koeffler HP. Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray. Exp Hematol. 2008 Nov;36(11):1471-9.

43: Goyama S, Yamamoto G, Shimabe M, Sato T, Ichikawa M, Ogawa S, Chiba S, Kurokawa M. Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells. Cell Stem Cell. 2008 Aug 7;3(2):207-20.

44: Nannya Y, Yokota H, Sato Y, Yamamoto G, Asai T, Ichikawa M, Watanabe T, Kumano K, Hangaishi A, Takahashi T, Chiba S, Yatomi Y, Kurokawa M. Molecular and cytogenetic response of chronic myelogenous leukemia treated with imatinib mesylate: one institutional experience in Japan. Int J Hematol. 2008 Sep;88(2):159-164.

45: Suzuki M, Kato M, Yuyan C, Takita J, Sanada M, Nannya Y, Yamamoto G, Takahashi A, Ikeda H, Kuwano H, Ogawa S, Hayashi Y. Whole-genome profiling of chromosomal aberrations in hepatoblastoma using high-density single-nucleotide polymorphism genotyping microarrays. Cancer Sci. 2008 Mar;99(3):564-70.

46: Kawase T, Nannya Y, Torikai H, Yamamoto G, Onizuka M, Morishima S, Tsujimura K, Miyamura K, Kodera Y, Morishima Y, Takahashi T, Kuzushima K, Ogawa S, Akatsuka Y. Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA. Blood. 2008 Mar 15;111(6):3286-94.

47: Ogawa S, Nanya Y, Yamamoto G. Genome-wide copy number analysis on GeneChip platform using copy number analyzer for affymetrix GeneChip 2.0 software. Methods Mol Biol. 2007;396:185-206.

48: Kawazu M, Yamamoto G, Yoshimi M, Yamamoto K, Asai T, Ichikawa M, Seo S, Nakagawa M, Chiba S, Kurokawa M, Ogawa S. Expression profiling of immature thymocytes revealed a novel homeobox gene that regulates double-negative thymocyte development. J Immunol. 2007 Oct 15;179(8):5335-45.

49: Yamamoto G, Nannya Y, Kato M, Sanada M, Levine RL, Kawamata N, Hangaishi A, Kurokawa M, Chiba S, Gilliland DG, Koeffler HP, Ogawa S. Highly sensitive method for genomewide detection of allelic composition in nonpaired, primary tumor specimens by use of affymetrix single-nucleotide-polymorphism genotyping microarrays. Am J Hum Genet. 2007 Jul;81(1):114-26.

50: Jacobs S, Thompson ER, Nannya Y, Yamamoto G, Pillai R, Ogawa S, Bailey DK, Campbell IG. Genome-wide, high-resolution detection of copy number, loss of heterozygosity, and genotypes from formalin-fixed, paraffin-embedded tumor tissue using microarrays. Cancer Res. 2007 Mar 15;67(6):2544-51.

51: Seo S, Asai T, Saito T, Suzuki T, Morishita Y, Nakamoto T, Ichikawa M, Yamamoto G, Kawazu M, Yamagata T, Sakai R, Mitani K, Ogawa S, Kurokawa M, Chiba S, Hirai H. Crk-associated substrate lymphocyte type is required for lymphocyte trafficking and marginal zone B cell maintenance. J Immunol. 2005 Sep 15;175(6):3492-501.

52: Kawazu M, Asai T, Ichikawa M, Yamamoto G, Saito T, Goyama S, Mitani K, Miyazono K, Chiba S, Ogawa S, Kurokawa M, Hirai H. Functional domains of Runx1 are differentially required for CD4 repression, TCRbeta expression, and CD4/8 double-negative to CD4/8 double-positive transition in thymocyte development. J Immunol. 2005 Mar 15;174(6):3526-33.

53: Yamaguchi Y, Kurokawa M, Imai Y, Izutsu K, Asai T, Ichikawa M, Yamamoto G, Nitta E, Yamagata T, Sasaki K, Mitani K, Ogawa S, Chiba S, Hirai H. AML1 is functionally regulated through p300-mediated acetylation on specific lysine residues. J Biol Chem. 2004 Apr 9;279(15):15630-8.

54: Saito T, Chiba S, Ichikawa M, Kunisato A, Asai T, Shimizu K, Yamaguchi T, Yamamoto G, Seo S, Kumano K, Nakagami-Yamaguchi E, Hamada Y, Aizawa S, Hirai H. Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development. Immunity. 2003 May;18(5):675-85.

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