Ryoichi Ono, MD, PhD.

[研究テーマ]

白血病発症の分子機構の解析

[業績]

-Original articles

(*, corresponding author)

1. Nakamura A, Masuya M, Shinmei M, Tawara I, Nosaka T, Ono R*. Bahcc1 is critical for the aberrant epigenetic program in a mouse model of MLL-ENL-mediated leukemia. Blood Adv. 8: 2193-2206, 2024.

2. Tharavecharak S, Fujimoto H, Yasuma T, D’Alessandro-Gabazza CN, Toda M, Tomaru A, Saiki H, Uemura M, Kogue Y, Ito T, Furuhashi K, Okano T, Takeshita A, Nishihama K, Ono R, Hataji O, Nosaka T, Kobayashi T, Gabazza, EC. Bleomycin-induced pulmonary fibrosis in transgenic mice carrying the human MUC5B rs35705950 variant. Cells 13: 1523, 2024.

3. D'Alessandro-Gabazza CN, Yasuma T, Kobayashi T, Toda M, Abdel-Hamid AM, Fujimoto H, Hataji O, Nakahara H, Takeshita A, Nishihama K, Okano T, Saiki H, Okano Y, Tomaru A, Fridman D'Alessandro V, Shiraishi M, Mizoguchi A, Ono R, Ohtsuka J, Fukumura M, Nosaka T, Mi X, Shukla D, Kataoka K, Kondoh Y, Hirose M, Arai T, Inoue Y, Yano Y, Mackie RI, Cann I, Gabazza EC. Inhibition of lung microbiota-derived proapoptotic peptides ameliorates acute exacerbation of pulmonary fibrosis. Nat. Commun. 13:1558, 2022.

4. Ohtsuka J, Imai M, Fukumura M, Maeda M, Eguchi A, Ono R, Maemura T, Ito M, Yamayoshi S, Kataoka Y, Kawaoka Y, Nosaka T. Non-propagative human parainfluenza virus type 2 nasal vaccine robustly protects the upper and lower airways against SARS-CoV-2. iScience 24:103379, 2021.

5. Ono R*, Masuya M, Inoue N, Shinmei M, Ishii S, Maegawa Y, Mahrjan BD, Katayama N, Nosaka T. Tet1 is not required for myeloid leukemogenesis by MLL-ENL in novel mouse models. PLOS ONE 16:e0248425, 2021.

6. Sawaki A, Miyazaki K, Yamaguchi M, Takeuchi T, Kobayashi K, Imai H, Tawara I, Ono R, Nosaka T, Katayama N. Genetic polymorphisms and vincristine-induced peripheral neuropathy in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Int. J. Hematol. 111: 686-691, 2020.

7. Maharjan BD, Ono R, Nosaka T. Eya2 is critical for the E2A-HLF-mediated immortalization of mouse hematopoietic stem/progenitor cells. Int. J. Oncol. 54:981-990, 2019.

8. Ono R*, Masuya M, Ishii S, Katayama N, Nosaka T. Eya2, a target activated by Plzf, is critical for PLZF-RARA-induced leukemogenesis. Mol. Cell. Biol., 37:e00585-16, 2017.

9. Takeuchi, T, Yamaguchi M, Kobayashi K, Miyazaki K, Tawara I, Imai H, Ono R, Nosaka T, Tanaka K, Katayama N. MYD88, CD79B, and CARD11 gene mutations in CD5-positive diffuse large B-cell lymphoma. Cancer, 123:1166-1173, 2017.

10. Kobayashi K, Yamaguchi M, Miyazaki K, Imai H, Yokoe K, Ono R, Nosaka T, Katayama N. Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features. Cancer Med., 5:1802-1809, 2016.

11. Ono R, Masuya M, Nakajima H, Enomoto Y, Miyata E, Nakamura A, Ishii S, Suzuki K, Shibata-Minoshima F, Katayama N, Kitamura T, Nosaka T. Plzf drives MLL-fusion-mediated leukemogenesis specifically in long-term hematopoietic stem cells. Blood, 122:1271-1283, 2013.

12. Shimozawa N, Ono R, Shimada M, Shibata H, Takahashi I, Inada H, Takada T, Nosaka T, Yasutomi Y. Cynomolgus monkey induced pluripotent stem cells established by using exogenous genes derived from the same monkey species. Differentiation, 85:131-139, 2013.

13. Liu B, Ohishi K, Orito Y, Nakamori Y, Nishikawa H, Ino K, Suzuki K, Matsumoto T, Masuya M, Hamada H, Mineno J, Ono R, Nosaka T, Shiku H, Katayama N. Manipulation of human early T lymphopoiesis by coculture on human bone marrow stromal cells: potential utility for adoptive immunotherapy. Exp. Hematol., 41:367-376, 2013.

14. Suzuki K, Ono R, Ohishi K, Masuya M, Kataoka I, Liu B, Nakamori Y, Ino K, Monma F, Hamada H, Kitamura T, Katayama N, Nosaka T. IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+hematopoietic cells on stromal cells. Int. J. Oncol., 40: 53-62, 2012.

15. Minobe K, Ono R, Matsumine A, Shibata-Minoshima F, Izawa K, Oki T, Kitaura J, Iino T, Takita J, Iwamoto S, Hori H, Komada Y, Uchida A, Hayashi Y, Kitamura T, Nosaka T. Expression of ADAMTS4 in Ewing's sarcoma. Int. J. Oncol., 37:569-581, 2010.

16. Ono R, Kumagai H, Nakajima H, Hishiya A, Taki T, Horikawa K, Takatsu K, Satoh T, Hayashi Y, Kitamura T, Nosaka T. Mixed-lineage-leukemia (MLL) fusion protein collaborates with Ras to induce acute leukemia through aberrant Hox expression and Raf activation. Leukemia, 23:2197-2209, 2009.

17. Jin G, Matsushita H, Asai S, Tsukamoto H, Ono R, Nosaka T, Yahata T, Takahashi S, Miyachi H. FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the repression of the ENT1 expression. Biochem. Biophys. Res. Commun., 390:1001-1006, 2009.

18. Watanabe-Okochi N, Oki T, Komeno Y, Kato N, Yuji K, Ono R, Harada Y, Harada H, Hayashi Y, Nakajima H, Nosaka T, Kitaura J, Kitamura T. Possible involvement of RasGRP4 in leukemogenesis. Int. J. Hematol., 89: 470-481, 2009.

19. Watanabe-Okochi N, Kitaura J, Ono R, Harada H, Harada Y, Komeno Y, Nakajima H, Nosaka T, Inaba T, and Kitamura T. AML1 mutations induced MDS and MDS/AML in a mouse BMT model. Blood, 111: 4297-4308, 2008.

20. Hiwatari M, Ono R, Taki T, Hishiya A, Ishii E, Kitamura T, Hayashi Y, and Nosaka T. Novel gain-of-function mutation in the extracellular domain of the PDGFRA gene in infant acute lymphoblastic leukemia with t(4;11)(q21;q23). Leukemia, 22: 2279-2280, 2008.

21. Matsushita H, Nakajima H, Nakamura Y, Tsukamoto H, Tanaka Y, Jin G, Yabe M, Asai S, Ono R, Nosaka T, Sugita K, Morimoto A, Hayashi Y, Hotta T, Ando K, and Miyachi H. C/EBPa and C/EBPe induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene. Oncogene, 27: 6749-6760, 2008.

22. Ono R, Nakajima H, Ozaki K, Kumagai H, Kawashima T, Taki T, Kitamura T, Hayashi Y & Nosaka T. Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple-lineage leukemogenesis. J. Clin. Invest., 115: 919-929, 2005.

23. Ono R, Ihara M, Nakajima H, Ozaki K, Kataoka-Fujiwara Y, Taki T, Nagata K, Inagaki M, Yoshida N, Kitamura T, Hayashi Y, Kinoshita M & Nosaka T. Disruption of Sept6, a fusion partner gene of MLL, does not affect ontogeny, leukemogenesis induced by MLL-SEPT6, or phenotype induced by the loss of Sept4. Mol. Cell. Biol., 25: 10965-10978, 2005.

24. Taki T, Akiyama M, Saito S, Ono R, Taniwaki M, Kato Y, Yuza Y, Eto Y & Hayashi Y. The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complex translocation involving chromosomes 7, 11, 19 and 22. Oncogene, 24: 5191-5197, 2005.

25. Ono R, Taki T, Taketani T, Kawaguchi H, Taniwaki M, Okamura T, Kawa K, Hanada R, Kobayashi M, & Hayashi Y. SEPTIN6, a human homolog to mouse Septin6, is fused to MLL in infant acute myeloid leukemia with complex chromosomal abnormalities involving 11q23 and Xq24. Cancer Res., 62: 333-337, 2002.

26. Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, & Hayashi Y. LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23). Cancer Res., 62: 4075-4080, 2002.

27. Taketani T, Taki T, Takita J, Ono R, Horikoshi Y, Kaneko Y, Sako M, Hanada R, Hongo T, & Hayashi Y. Mutation of the AML1/RUNX1 gene in a transient myeloproliferative disorder patient with Down syndrome. Leukemia, 16: 1866-1867, 2002.

28. Taketani T, Taki T, Ono R, Kobayashi Y, Ida K, & Hayashi Y. The chromosome translocation t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9. Genes Chromosomes Cancer, 34: 437-443, 2002.

29. Yamamoto K, Nagata K, Tsurukubo Y, Inagaki K, Ono R, Taki T, Hayashi Y, & Hamaguchi H. Translocation (8;12)(q13;p13) during disease progression in acute myelomonocytic leukemia with t(11;19)(q23;p13.1). Cancer Genet. Cytogenet., 137: 64-67, 2002.

-Review articles/ Book Chapters

1. 小埜良一. 第6章 SECTION4 慢性骨髄性白血病．In: 山本将平、康勝好 編著．小児血液疾患診療マニュアル 中外医学社刊 p193-199, 2025.

2. 小埜良一. 誘導型生体内白血病発症マウスモデルを用いた、エピジェネティック制御経路を介する発がん分子機構の解析. Medical Science Digest 55巻11: 626-628, 2024.

3. 小埜良一、野阪哲哉. 血液腫瘍モデル動物の現状と展望. 日本臨床 78巻増刊3: 152-158, 2020.

4. Kitamura T, Watanabe-Okochi N, Enomoto Y, Nakahara F, Oki T, Komeno Y, Kato N, Doki N, Uchida T, Kagiyama Y, Togami K, Kawabata KC, Nishimura K, Hayashi Y, Nagase R, Saika M, Fukushima T, Asada S, Fujino T, Izawa Y, Horikawa S, Fukuyama T, Tanaka Y, Ono R, Goyama S, Nosaka T, Kitaura J, & Inoue D. Novel working hypothesis for pathogenesis of hematological malignancies: combination of mutations-induced cellular phenotypes determines the disease (cMIP-DD). J. Biochem. 159:17-25, 2016.

5. 野阪哲哉、小埜良一. MLL融合遺伝子による白血病発症機構. 血液・腫瘍科, 61:217-223, 2010.

6. 小埜良一．MLL遺伝子再構成を有する小児白血病発症の分子機構．日小血会誌，21: 111-120, 2007.

7. 小埜良一，野阪哲哉．MLL関連白血病の分子病態．血液・腫瘍科，52: 615-624, 2006.

8. Ono R, Nosaka T, & Hayashi Y. Roles of a trithorax group gene, MLL, in hematopoiesis. Int J Hematol., 81: 288-293, 2005.

[所属学会]

日本血液学会（2021年より評議員）、日本癌学会、日本小児血液・がん学会

日本小児科学会、日本人類遺伝学会、日本ウイルス学会

[学術上の栄誉]

2002年　日本血液学会奨励賞

2007年　日本白血病研究基金 一般研究賞

2019年　三医会 緑の風記念三重医学研究振興会賞