基礎研究

リンパ系腫瘍グループ

血液がんの中でも特に診断及び治療が難しい病気の一つが、悪性リンパ腫です。特にT細胞性リンパ腫は既存の治療法に抵抗性で、あるいは、一度は治療が奏功しても高頻度に再発をきたします。この現状を変えて行くために、新しい治療標的分子の同定、分子標的薬の開発が必要です。

我々は2017年より基盤となるべき分子病態について解析してきました。次世代シークエンサーの登場によりT細胞性リンパ腫の複雑な体細胞遺伝子変異が明らかになった一方で (Nakagawa et al. JEM 211:2497-505, 2014.など)、どの遺伝子を標的にすれば治療効果をあげられるのかは別の機能的解析が必要です。がんは一つの遺伝子異常ではなく、たくさんの遺伝子群によるnet effectで腫瘍形質を維持します。ある遺伝子を標的としても、ほかの遺伝子がその機能を代替してしまえば、不十分な効果しか得られないこともあります。

より効果的な治療標的を見つけるために、我々はCRISPR/Cas9網羅的遺伝子ノックアウトスクリーニングを基盤とした仕事を進めてきました。我々はこのシステムをヒトT細胞性リンパ腫細胞株に導入し、約 20000遺伝子の中から網羅的な探索を行っています（図）。これらの成果はCancer Cell, Bloodといったトップジャーナルで発表してきました。さらに我々の研究成果を、創薬、治療反応性バイオマーカー、薬剤耐性克服へ発展させ、実医療へ貢献することを目指しています。

代表的論文

1. Nakagawa, M., Shaffer, AL., Ceribelli, M., Zhang, M., Wright, GW., Huang, da W., Xiao, W., Powell, J., Petrus, MN., Yang, Y., Phelan, JD., Kohlhammer, H., Dubois, SP., Yoo, HM., Bachy, E., Webster, DE., Yang, Y., Xu, W., Yu, X., Zhao, H., Bryant, BR., Shimono, J., Ishio, T., Maeda, M., Green, PL., Waldmann, TA. and Staudt, LM. Targeting the HTLV-I-regulated BATF3/IRF4 Transcriptional Network in Adult T-Cell Leukemia/Lymphoma. Cancer Cell, 34:286-297, 2018.
   
   shRNAライブラリースクリーニングとCRISPRライブラリースクリーニングを駆使してT細胞性リンパ腫の一病型である成人T細胞白血病リンパ腫においてBATF3/IRF4が重要な治療標的であることを見出しました。成人T細胞白血病リンパ腫の原因ウイルスであるHTLV-IがBATF3の発現に関わることで、ウイルスと腫瘍発生の関係性についても明らかにしました。
   
   
2. Ishio, T., Kumar, S., Shimono, J., Daenthanasanmak, A., Dubois, S., Lin, Y., Bryant, BR., Petrus, MN., Bachy, E., Huang, DW., Yang, Y., Green, PL., Hasegawa, H., Maeda, M., Goto, H., Endo, T., Yokota, T., Hatanaka, KC., Hatanaka, Y., Tanaka, S., Matsuno, Y., Yang, Y., Hashino, S., Teshima, T., Waldmann, TA., Staudt, LM., Nakagawa, M. Genome-wide CRISPR screen identifies CDK6 as a therapeutic target in Adult T-cell leukemia/lymphoma. Blood. 139:1541-1556, 2022.
   
   石尾先生が大学院生としてCRISPRライブラリースクリーニングの解析を進めてくださり、成人T細胞白血病リンパ腫においてCDK6が重要な治療標的であることを見出しました。CDK6はキナーゼであり、その阻害薬は成人T細胞白血病リンパ腫に有効である可能性を指摘しました。
   
   
3. Chiba, M., Shimono, J., Ishio, T., Takei, N., Kasahara, K., Ogasawara, R., Ara, T., Goto, H., Izumiyama, K., Otsuguro, S., Perera, LP., Hasegawa, H., Maeda, M., Hashino, S., Maenaka, K., Teshima, T., Waldmann, TA., Yang, Y., Nakagawa, M. Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas. Blood. 140:1951-1963, 2022.
   
   千葉先生が大学院生として解析して下さった仕事です。成人T細胞白血病リンパ腫はCD48という分子の発現を減少させることで、NK細胞による腫瘍監視機構から逃れることを見出しました。
   
   
4. Chiba, M., Shimono, J., Suto, K., Ishio, T., Endo, T., Goto, H., Hasegawa, H., Maeda, M., Teshima, T., Yang, Y., Nakagawa, M. Whole-genome CRISPR screening identifies molecular mechanisms of PD-L1 expression in adult T-cell leukemia/lymphoma. Blood. 143:1379-1390., 2024
   
   下埜先生が初期の実験を担当され、その後千葉先生が仕事を引き継がれ、まとめて下さった仕事です（co-first author）。T細胞性リンパ腫のPD-L1発現維持機構を明らかにし、さらにPD-L1を治療標的とするキメラ抗原受容体遺伝子改変T細胞（CAR-T）細胞を開発しました。

獲得競争的研究費

• 2017年　公益財団法人 先進医薬研究振興財団　血液医学分野研究助成金
• 2017年　公益財団法人 武田科学振興財団　医学系研究奨励
• 2018年　日本学術振興会科学研究費助成事業　基盤研究(C)
• 2018年　日本白血病研究基金 一般研究賞
• 2018年　寿原記念財団 研究助成
• 2018年　高松宮妃癌研究基金　研究助成金
• 2019年　公益財団法人 アステラス病態代謝研究会　研究助成金
• 2021年　日本学術振興会科学研究費助成事業　基盤研究(B)
• 2024年　日本学術振興会科学研究費助成事業　基盤研究(B)

Lymphoid Malignancies Group

RESEARCH INTERESTS

Functional genomics for discovering the therapeutic molecular targets in PTCL

> Identifying the "Achilles' heel" genes in peripheral T-cell lymphomas as molecular targets for therapeutic intervention.
> Defining the molecular mechanisms of frequently mutated CCR4 gene in PTCL.

Overview

Human peripheral T-cell lymphomas (PTCL) is approximately 10 % of non-Hodgkin Lymphomas in worldwide. PTCL comprises heterogeneous diseases, most of which are aggressive with less than 40% of 5-year overall survival with current treatment strategy. The discovery of new therapeutic modalities is urgently needed.

Recently, the Next generation sequencing technology has enabled us to find frequently mutated genes in PTCL. In my previous work as a postdoctoral fellow in Lou Staudt Lab and Thomas Waldmann lab, we discovered frequent gain-of-function mutations in the chemokine receptor CCR4 gene in adult T-cell leukemia/lymphoma (ATLL) and provided functional evidence that inhibition of CCR4 signaling might have therapeutic potential for patients with ATLL. However most of the other somatically mutated genes in PTCL have not been fully characterized in terms of therapeutic targets.
On the other hand, it has recently been known that the malignant cells potentially acquire the dependence on un-mutated genes which is the phenomenon called as "non-oncogene addiction". These observations suggest that an non-biased and comprehensive functional investigation should be performed in order to discover the therapeutic molecular targets in PTCL.

The goal of our laboratory is to understand the oncogenic molecular networks in PTCL that can be exploited for therapeutic intervention. To directly address this issue, our lab is applying the revolutionizing CRISPR/Cas9/sgRNA library screening technology to the following functional investigation.

1) Identifying indispensable pathways/molecules for the cellular proliferation/survival/immune evasion of PTCL cells, especially ATLL. 

2) Discovering the novel drugs/cellular therapies targeting PTCL cells.

PUBLICATION LIST

1. Chiba, M., Shimono, J., Suto, K., Ishio, T., Endo, T., Goto, H., Hasegawa, H., Maeda, M., Teshima, T., Yang, Y., Nakagawa, M. Whole-genome CRISPR screening identifies molecular mechanisms of PD-L1 expression in adult T-cell leukemia/lymphoma. Blood. 143:1379-1390., 2024.
2. Vaswani, PPM., Onozawa, M., Hasegawa, Y., Ohigashi, H., Ara, T., Matsukawa, T., Yasumoto, A., Shiratori, S., Goto, H., Nakagawa, M., Kahata, K., Endo, T., Hashimoto, D., Teshima, T. Incidence and course of Epstein-Barr virus viremia after allogeneic hematopoietic stem cell transplant for adult-onset systemic chronic active Epstein-Barr virus disease. Bone Marrow Transplant. 2023 In press. 
3. Song, Z., Wu, W., Wei, W., Xiao, W., Lei, M., Cai, K., Huang, DW., Jeong, S., Zhang, JP., Wang, H., Kadin, ME., Waldmann, TA., Staudt, LM., Nakagawa, M., Yang, Y. Analysis and Therapeutic Targeting of the IL-1R Pathway in Anaplastic Large Cell Lymphoma. Blood. 2023 In press.
4. Ara, T., Endo, T., Goto, H., Kasahara, K., Hasegawa, Y., Yokoyama, S., Shiratori, S., Nakagawa, M., Kuwahara, K., Takakuwa, E., Hashino, S., Teshima, T. Antiretroviral therapy achieved metabolic complete remission of hepatic AIDS related Epstein-Barr virus-associated smooth muscle tumor. Antivir Ther. 27:13596535221126828、2022.
5. Wei, W., Song, Z., Chiba, M., Wu, W., Jeong, S., Zhang, JP., Kadin, ME., Nakagawa, M., Yang, Y. Analysis and therapeutic targeting of the EP300 and CREBBP acetyltransferases in anaplastic large cell lymphoma and Hodgkin lymphoma. Leukemia. 37:396-407, 2022.
6. Chiba, M., Shimono, J., Ishio, T., Takei, N., Kasahara, K., Ogasawara, R., Ara, T., Goto, H., Izumiyama, K., Otsuguro, S., Perera, LP., Hasegawa, H., Maeda, M., Hashino, S., Maenaka, K., Teshima, T., Waldmann, TA., Yang, Y., Nakagawa, M. (Corresponding author) Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas. Blood. 140:1951-1963, 2022.
7. Zhang, Z., Hasegawa, Y., Hashimoto, D., Senjo, H., Kikuchi, R., Chen, X., Yoneda, K., Sekiguchi, T., Kawase, T., Tsuzuki, H., Ishio, T., Ara, T., Ohigashi, H., Nakagawa, M., Teshima, T. Gilteritinib enhances graft-versus-leukemia effects against FLT3-ITD mutant leukemia after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 57:775-780, 2022.
8. Ishio, T., Kumar, S., Shimono, J., Daenthanasanmak, A., Dubois, S., Lin, Y., Bryant, BR., Petrus, MN., Bachy, E., Huang, DW., Yang, Y., Green, PL., Hasegawa, H., Maeda, M., Goto, H., Endo, T., Yokota, T., Hatanaka, KC., Hatanaka, Y., Tanaka, S., Matsuno, Y., Yang, Y., Hashino, S., Teshima, T., Waldmann, TA., Staudt, LM., Nakagawa, M. (Corresponding author) Genome-wide CRISPR screen identifies CDK6 as a therapeutic target in Adult T-cell leukemia/lymphoma. Blood. 139:1541-1556, 2022.
9. Wang, H., Wei, W., Zhang, JP., Song, Z., Li, Y., Xiao, W., Liu, Y., Zeng, MS., Petrus, MN., Thomas, CJ., Kadin, ME., Nakagawa, M., Waldmann, TA., Yang, Y. A novel model of alternative NF-kappaB pathway activation in anaplastic large cell lymphoma. Leukemia, 35:1976-1989, 2021.
10. Shiratori, S., Ohigashi, H., Ara, T., Yasumoto, A., Goto, H., Nakagawa, M., Sugita, J., Onozawa, M., Kahata, K., Endo, T., Hashimoto, D., Teshima, T. High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease. Ann Hematol. 100:1321-1328, 2021.
11. Hidaka, D., Onozawa, M., Miyashita, N., Yokoyama, S., Nakagawa, M., Hashimoto, D., Teshima, T. Short-term treatment with imetelstat sensitizes hematopoietic malignant cells to a genotoxic agent via suppression of the telomerase-mediated DNA repair process. Leuk Lymphoma. 61:2722-2732, 2020.
12. Shiratori S, Ohigashi H, Takahashi S, Ara T, Goto H, Nakagawa M, Sugita J, Onozawa M, Kahata K, Endo T, Hashimoto D, Teshima T; North Japan Hematology Study Group (NJHSG). Reduced dose of MTX for GVHD prophylaxis promotes engraftment and decreases non-relapse mortality in umbilical cord blood transplantation. Ann Hematol. 99:591-598, 2020.
13. Zhang, JP., Song, Z., Wang, HB., Lang, L., Yang YZ., Xiao, W., Webster, DE., Wei, W., Barta, SK., Kadin, ME., Staudt, LM., Nakagawa, M., and Yang, Y. (Co-corresponding author) A novel model of controlling PD-L1 expression in ALK+ Anaplastic Large Cell Lymphoma. Blood, 132:171-185, 2019. 
14. Ohigashi, H., Hashimoto, D., Hayase, E., Takahashi, S., Ara, T., Yamakawa, T., Sugita, J., Onozawa, M., Nakagawa, M., Teshima, T. Ocular instillation of vitamin A-coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD. Blood Adv. 3:1003-1010, 2019
15. Hidaka, D., Onozawa, M., Hashiguchi, J., Miyashita, N., Kasahara, K., Fujisawa, S., Hayase, E., Okada, K., Shiratori, S., Goto, H., Sugita, J., Nakagawa, M., Hashimoto, D., Kahata, K., Endo, T., Yamamoto, S., Tsutsumi, Y., Haseyama, Y., Nagashima, T., Mori, A., Ota, S., Sakai, H., Ishihara, T., Imai, K., Miyagishima, T., Kakinoki, Y., Kurosawa, M., Kobayashi, H., Iwasaki, H., Shimizu, C., Kondo, T., Teshima, T. 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. Clin Lymphoma Myeloma Leuk. 18:e469-e479, 2018
16. 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. The association between the incidence of intestinal graft-vs-host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation. Clin Transplant. 32:e13361, 2018
17. Nakagawa, M., Shaffer, AL., Ceribelli, M., Zhang, M., Wright, GW., Huang, da W., Xiao, W., Powell, J., Petrus, MN., Yang, Y., Phelan, JD., Kohlhammer, H., Dubois, SP., Yoo, HM., Bachy, E., Webster, DE., Yang, Y., Xu, W., Yu, X., Zhao, H., Bryant, BR., Shimono, J., Ishio, T., Maeda, M., Green, PL., Waldmann, TA. and Staudt, LM. Targeting the HTLV-I-regulated BATF3/IRF4 Transcriptional Network in Adult T-Cell Leukemia/Lymphoma. Cancer Cell, 34:286-297, 2018. 
18. Phelan, JD., Young, RM., Webster, DE., Roulland, S., Wright, GW., Kasbekar, M., Shaffer, AL., Ceribelli, M., Wang, JQ., Schmitz, R., Nakagawa, M., Bachy, E., Huang, da W., Ji, Y., Chen, L., Yang, Y., Zhao, H., Yu, X., Xu, W., Palisoc, MM., Valadez, RR., Davies-Hill, T., Wilson, WH., Chan, WC., Jaffe, ES., Gascoyne, RD, Campo, E., Rosenwald, A., Ott, G., Delabie, J., Rimsza, LM, Rodriguez, FJ., Estephan, F., Holdhoff, M., Kruhlak, MJ., Hewitt, SM., Thomas, CJ., Pittaluga, S, Oellerich, T., and Staudt, LM. A Multiprotein Supercomplex Controlling Oncogenic Signaling in Lymphoma. Nature, 560:387-391, 2018.
19. Hashiguchi J, Onozawa M, Oguri S, Fujisawa S, Tsuji M, Okada K, Nakagawa, M., Hashimoto D, Kahata K, Kondo T, Shimizu C, Teshima T. Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia.  J Mol Diagn. 20:446-454, 2018. 
20. Ishio T, Sugita J, Tateno T, Hidaka D, Hayase E, Shiratori S, Okada K, Goto H, Onozawa M, Nakagawa, M., Hashimoto D, Kahata K, Fujimoto K, Endo T, Kondo T, Teshima T. Hematogones predict better outcome in allogeneic hematopoietic stem cell transplantation irrespective of graft sources. Biol Blood Marrow Transplant. 2018 Jun 14. pii: S1083-8791(18)30323-9.
21. Miyashita, N., Onozawa, M., Hayasaka, K., Yamada, T., Migita, O., Hata, K., Okada, K., Goto, H., Nakagawa, M., Hashimoto, D., Kahata, K., Kondo, T., Kunishima, S., Teshima, T. A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction. Ann Hematol. 97;629-640, 2018. 
22. Shiratori S, Kosugi-Kanaya M, Hayase E, Okada K, Goto H, Sugita J, Onozawa M, Nakagawa, M., Kahata K, Hashimoto D, Endo T, Kondo T, Teshima T. T-cell depletion effects of low-dose antithymocyte globulin for GVHD prophylaxis in HLA-matched allogeneic peripheral blood stem cell transplantation.Transpl Immunol. 46:21-22, 2018.
23. Tateno T, Onozawa M, Hashiguchi J, Ishio T, Yuzawa S, Matsuoka S, Kosugi-Kanaya M, Okada K, Shiratori S, Goto H, Kimura T, Sugita J, Nakagawa, M., Hashimoto D, Kahata K, Fujimoto K, Endo T, Kondo T, Tanaka S, Hashino S, Teshima T. Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images. Transpl Infect Dis. 19. doi: 10.1111/tid.12720, 2017. 
24. Perera, LP., Zhang, M., Nakagawa, M., Petrus, MN., Maeda, M., Kadin, ME., Waldmann, TA., Perera, PY. Chimeric antigen receptor modified T cells that target chemokine receptor CCR4 as a therapeutic modality for T-cell malignancies. American Journal of Hematology, 92:892-901, 2017.
25. Chen, J., Zhang. Y,, Petrus, MN., Xiao, W., Nicolae, A., Raffeld, M., Pittaluga, S., Bamford, RN., Nakagawa, M.,  Ouyanga, S., Epsteine, AL., Kadin, ME., Del Mistro, A.,  Woessnerh, R., Jaffe, ES., Waldmann, TA. Cytokine receptor signaling is required for the survival of ALK- anaplastic large cell lymphoma even in the presence of JAK1/STAT3 mutations. Proc. Natl. Acad. Sci. U S A, 114:3975-3980, 2017. 
26. Yang, Y., Kelly, P., Shaffer, AL., Schmitz, R., Yoo, HM., Liu, X., Huang, da W., Webster, D., Young, RM., Nakagawa, M., Ceribelli, M., Wright, GW., Yang, Y., Zhao, H., Yu, X., Xu, W., Chan, WC., Jaffe, ES., Gascoyne, RD., Campo, E., Rosenwald, A, Ott, G., Delabie, J., Rimsza, L., Staudt, LM.　 Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma.　 Cancer Cell, 29:494-507, 2016.
27. Hodson, DJ., Shaffer, AL., Xiao, W., Wright, GW., Schmitz, R., Phelan, JD., Yang, Y., Webster, DE., Rui, L., Kohlhammer, H., Nakagawa, M., Waldmann, TA., Staudt, LM. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2. Proc. Natl. Acad. Sci. U S A, 113:E2039-46, 2016. 
28. Nakagawa, M., Schmitz, R., Xiao, W., Goldman, CK., Yang, Y., Xu, W., Yu, X., Waldmann, TA., Staudt, LM. Gain-of-Function CCR4 Mutations in Adult T-cell Leukemia/Lymphoma. J. Exp. Med., 211:2497-505, 2014. 
29. Yu, P., Petrus, MN., Ju, W., Zhang, M., Conlon, KC., Nakagawa, M., Maeda, M., Bamford, RN., Waldmann, TA. Augmented efficacy with the combination of blockade of the Notch-1 pathway, bortezomib and romidepsin in a murine MT-1 adult T-cell leukemia model. Leukemia, 29:556-66, 2014. 
30. Suguro, M., Yoshida, N., Umino, A., Kato, H., Tagawa, H., Nakagawa, M., Fukuhara, N., Karnan, S., Takeuchi, I., Hocking, TD., Arita, K., Karube, K., Tsuzuki, S., Nakamura, S., Kinoshita, T., Seto, M. Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis. Cancer Sci., 105:897-904, 2014.
31. Karube, K., Nakagawa, M., Tsuzuki, S., Takeuchi, I., Honma, K., Nakashima, Y., Shimizu, N., Ko, YH., Morishima, Y., Ohshima, K., Nakamura, S., Seto, M. Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses. Blood, 118: 3195-204, 2011.
32. Nakagawa, M., Tsuzuki, S, Honma, K., Taguchi, O., Seto, M. Synergistic effect of Bcl2, Myc and Ccnd1 transforms mouse primary B-cells into malignant cells. Haematologica, 96: 1318-1326, 2011.
33. Umino, A., Nakagawa, M., Utsunomiya, A., Tsukasaki, K., Taira, N., Katayama, N., Seto, M. Clonal evolution of adult T-cell leukemia/lymphoma takes place in lymph node. Blood, 117: 5473-5478, 2011.
34. Kato, H., Kagami, Y., Nakagawa, M., Karnan, S., Yatabe, Y., Nakamura, S., Morishima, Y., Seto, M. IL-4/CD40L Co-Stimulation Induces Long-Term Proliferation for CD10-Positive Germinal Center B Cell-Like Diffuse Large B-Cell Lymphoma. The Open Leukemia Journal, 3: 60-68, 2010.
35. Seto, M., Honma, K., Nakagawa, M. Diversity of genome profiles in malignant lymphoma.   Cancer Sci., 101: 573-578, 2010.
36. Honma, K. Tsuzuki, S. Nakagawa,　M., Tagawa, H., Nakamura, S., Morishima, Y., Seto, M. TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas.    Blood, 114: 2467-2475, 2009.
37. Nakagawa, M., Nakagawa-Oshiro, A., Karnan, S., Tagawa, H., Utsunomiya, A., Nakamura, S., Takeuchi, I., Ohshima, K., Seto, M. Array CGH analysis of PTCL-U reveals a distinct subgroup with genetic alterations similar to lymphoma-type ATLL.    Clin. Cancer Res., 15: 30-38, 2009.
38. Takeuchi, I., Tagawa, H., Tsujikawa, A., Nakagawa, M., Katayama-Suguro, M., Guo, Y., Seto, M. 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.   Haematologica, 94: 61-69, 2009.
39. Hashino, S., Kobayashi, S., Takahata, M., Onozawa, M., Nakagawa, M., Kawamura, T., Fujisawa, F., Izumiyama, K., Kahata, K., Kondo, T., Asaka, M. Graft-versus-tumor effect after reduced-intensity allogeneic hematopoietic stem cell transplantation in a patient with advanced colon cancer.   Int. J. Clin. Oncol., 13: 176-180, 2008.
40. 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. Administration of micafungin as prophylactic antifungal therapy in patients undergoing allogeneic stem cell transplantation.   Int. J. Hematol., 87: 91-97, 2008.
41. Honma, K., Tsuzuki, S., Nakagawa, M., Karnan, S., Aizawa, Y., Kim, WS., Kim, YD., Ko, YH., Seto, M. TNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphoma.   Genes Chrom. Cancer, 47: 1-7, 2008.
42. Nakagawa, M., Hashino, S., Takahata, M., Kawamura, T., Fujisawa, F., Kahata, K., Kondo, T., Imamura, M., Ando, S., Asaka, M.   Successful reduced-intensity stem cell transplantation with cord blood for a poor-prognosis adult with refractory chronic active epstein-barr virus infection.   Int. J. Hematol., 85: 443-445, 2007.
43. Fukuhara, N., Nakamura, T., Nakagawa, M., Tagawa, H., Takeuchi, I., Yatabe, Y., Morishima, Y., Nakamura, S., Seto, M.   Chromosomal imbalances are associated with outcome of Helicobacter pylori eradication in t(11;18)(q21;q21) negative gastric MALT lymphomas.   Genes Chrom. Cancer, 46: 784-790, 2007.
44. Onozawa, M., Hashino, S., Takahata, M., Fujisaw, F., Kawamura, T., Nakagawa, M., Kahata, K., Kondo, T., Ota, S., Tanaka, J., Imamura, M., Asaka, M.   Relationship between preexisting anti-varicella-zoster virus (VZV) antibody and clinical VZV reactivation in hematopoietic stem cell transplantation recipients.   J. Clin. Microbiol., 44: 4441-4443, 2006.
45. Nakagawa, M., Seto, M., Hosokawa, Y.   Molecular pathogenesis of MALT lymphoma: two signaling pathways underlying anti-apoptotic effect of API2-MALT1 fusion protein.   Leukemia, 20: 929-936, 2006.
46. Nakagawa, M., Hosokawa, Y., Yonezumi, M., Izumiyama, K., Suzuki, R., Tsuzuki, S., Asaka, M., Seto, M.   MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10.   Blood, 106: 4210-4216, 2005.
47. Hosokawa, Y., Suzuki, H., Nakagawa, M., Lee, T.H., Seto, M.   API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-kappaB binding elements: Evidence for a positive feed-back loop pathway resulting in unremitting NF-kappaB activation.   Biochem. Biophys. Res. Commun., 334: 51-60, 2005.
48. Nakagawa, M., Kameoka, Y., Suzuki, R.   Nucleophosmin in acute myelogenous leukemia.   N. Engl. J. Med., 352: 1819-1820, 2005.
49. Izumiyama, K., Nakagawa, M., Yonezumi, M., Kasugai, Y., Suzuki, R., Suzuki, H., Tsuzuki, S., Hosokawa, Y., Asaka, M., Seto, M.   Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18) (q21;q21) MALT lymphoma.   Oncogene, 22: 8085-8092, 2003.
50. Nakagawa, M., Miyagishima, T., Kamata, T., Arai, S., Miura, Y., Onishi, S., Kishimoto, A., Kamishima, Y., Choi, G.H., Kudo, M., Okabe, M.   Refractory idiopathic cold agglutinin disease successfully treated with intermittent high-dose cyclophosphamide.   Rinsho Ketsueki, 42: 713-715, 2001.