Annual Report 2024

Division of Molecular Oncology

Keisuke Kataoka, Yasunori Kogure, Yuki Saito, Fumie Ueki, Yoko Hokama, Yoshiko Ito, Kayo Miura, Junji Koya, Koichi Murakami, Kentaro Yamaguchi, Sara Horie, Tomohiko Tanigawa, Kota Mizuno, Yosuke Mizukami, Haryoon Kim, Yusuke Kubota, Ami Inokuchi, Zen Tamura

Introduction

 The advent of next-generation sequencing (NGS) technologies has enabled us to delineate the genetic landscape of human cancers. We have worked on the integrated genetic analysis of diverse cancer types, especially on hematologic malignancies using cutting-edge genomic techniques.

The Team and What We Do

 By combining genomics (such as whole-genome sequencing and multi-omics single-cell analysis) with molecular and functional approaches (such as CRISPR screening), we aim to:

1. Genetically dissect the molecular pathogenesis of human cancers.

2. Identify novel potential therapeutic targets and/or biomarkers.

3. Establish the clinical relevance of genetic alterations.

Research Activities

 We conducted a genomic analysis of patients with extranodal NK/T-cell lymphoma (ENKTCL) in a Japan–France collaborative study and identified recurrent alterations in several X-chromosome genes, including MSN, BCOR, DDX3X, and KDM6A (Ito Y, Cancer Res, 2024). Building upon these findings, we developed a novel mouse model that spontaneously develops NK-cell lymphomas (Koya J, Nat Commun, 2024). This model recapitulates key features of human ENKTCL, including the development of tumors in characteristic organs such as the salivary glands. Using this model, we demonstrated that the cell of origin of NK-cell lymphomas is tissue-resident NK cells and identified novel therapeutic targets such as KLRG1. Additionally, a gene panel for hematologic malignancies co-developed with Otsuka Pharmaceutical, named “HemeSight”, has received regulatory approval for manufacturing and marketing as well as national insurance coverage in Japan.

Future Prospects

 As shown in the above, we aim to delineate the entire picture of genetic aberrations in human cancers using cutting-edge genomic techniques. Based on the genetic findings, we will identify novel potential drug targets and/or biomarkers and clarify the molecular pathogenesis underlying cancer development and progression. In addition, we will establish the clinical significance of these alterations, which will help the advancement of cancer precision medicine.

List of papers published in 2024

Journal

1. Fujioka M, Itonaga H, Nakazawa H, Nishida T, Kataoka K, Ikeda T, Kako S, Matsuoka KI, Adachi K, Fujiwara SI, Aotsuka N, Kawakita T, Sakaida E, Kanda Y, Ichinohe T, Atsuta Y, Miyazaki Y, Ishiyama K. Superior Survival After Unrelated Allogeneic Stem Cell Transplantation With Low-Dose ATG Compared to Low-Dose TBI in Myeloablative Fludarabine/Busulfan-Based Regimen for MDS on Behalf of the Adult MDS Working Group of the JSTCT. Transplantation and cellular therapy, 31:18.e1-18.e12, 2025

2. Goto H, Kumode T, Mishima Y, Kataoka K, Ogawa Y, Kanemura N, Shimada K, Uchida T, Kuroe Y, Kawasaki A, Sato J, Teshima T. Efficacy and safety of mosunetuzumab monotherapy for Japanese patients with relapsed/refractory follicular lymphoma: FLMOON-1. International journal of clinical oncology, 30:389-396, 2025

3. Yamada S, Satou A, Tsuyuki Y, Iba S, Okumura Y, Ishikawa E, Ito H, Kogure Y, Goto N, Tanikawa M, Shimada K, Tsukamoto T, Karube K, Yokoo H, Kataoka K, Tomita A, Mase M, Nakamura S. Primary large B-cell lymphoma of the central nervous system: A reappraisal of CD5-positive cases based on clinical, pathological, and molecular evaluation. Pathology international, 75:11-20, 2025

4. Hosoba R, Fukuhara S, Kogure Y, Takano K, Shibata M, Horiuchi T, Kobayashi S, Makita S, Iwaki N, Munakata W, Maeshima AM, Kimura F, Kataoka K, Izutsu K. Whole exome sequencing analysis of a patient with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions with ETV6::LYN fusion gene. Annals of hematology, 104:809-813, 2025

5. Masuda K, Sakurai M, Shiozawa Y, Sakamoto M, Shindo T, Inokuchi A, Hayashi H, Koda Y, Nagata H, Kato J, Kataoka K. Successful Antibiotic Treatment of Phlegmonous Gastritis Following Allogeneic Hematopoietic Stem Cell Transplantation. Internal medicine (Tokyo, Japan), 2025

6. Sugimoto M, Yagasaki K, Matsuki E, Shimizu T, Sakurai M, Kataoka K, Doorenbos AZ. Unmet Needs and Health-Related Quality of Life Among Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: A Mixed-Methods Study. Psycho-oncology, 34:e70103, 2025

7. Kobayashi T, Ishizawa K, Machida R, Sadachi R, Sasaki K, Kim H, Kataoka K, Munakata W, Fukuhara N, Nagai H. Obinutuzumab maintenance versus observation for patients with newly diagnosed high tumor burden follicular lymphoma who achieved complete metabolic response after obinutuzumab plus bendamustine induction therapy: a multicenter, randomized, phase III study (JCOG2008, MAIN study). Japanese journal of clinical oncology, 55:666-671, 2025

8. Fujimoto A, Sakata S, Kataoka K, Kogure Y, Chiba K, Okada A, Shiraishi Y, Baba S, Maruyama D, Ogawa S, Takeuchi K. High-accuracy Detection of PD-L1 3'-UTR Disruption by Immunohistochemistry and Fluorescence in Situ Hybridization on Formalin-fixed Paraffin-embedded Sections. The American journal of surgical pathology, 49:490-498, 2025

9. Kogure Y, Kataoka K. Clinical and therapeutic significance of genetic profiling in adult T-cell leukemia/lymphoma. Leukemia research, 151:107676, 2025

10. Shinohara A, Shindo M, Yamasaki S, Kato K, Yoshihara S, Yamamoto G, Kataoka K, Ikeda T, Kobayashi H, Serizawa K, Mori Y, Takayama N, Nakazawa H, Ito A, Katayama Y, Kanda Y, Yoshimitsu M, Fukuda T, Atsuta Y, Kondo E. Fludarabine Plus Myeloablative Dose of Busulfan Regimen Was Associated with High Nonrelapse Mortality in Allogeneic Hematopoietic Stem Cell Transplantation for Malignant Lymphoma: A Propensity Score-Matched Comparison Study with Fludarabine Plus High-Dose Melphalan. Transplantation and cellular therapy, 31:382.e1-382.e17, 2025

11. Koresawa-Shimizu R, Suzuki R, Uehara Y, Hiramoto N, Sawa M, Fukuda T, Kataoka K, Kanda Y, Oyake T, Kubota Y, Uchida N, Yano S, Kobayashi H, Tanaka J, Atsuta Y, Kondo E. Comparison of MEAM, MCEC and LEED high-dose chemotherapy followed by autologous stem cell transplantation in relapsed/refractory diffuse large B-cell lymphoma: data from the Japan Society for Hematopoietic and Cellular Therapy Registry. Bone marrow transplantation, 59:125-127, 2024

12. Saito S, Saito Y, Sato S, Aoki S, Fujita H, Ito Y, Ono N, Funakoshi T, Kawai T, Suzuki H, Sasaki T, Tanaka T, Inoie M, Hata K, Kataoka K, Kosaki K, Amagai M, Nakabayashi K, Kubo A. Gene-specific somatic epigenetic mosaicism of FDFT1 underlies a non-hereditary localized form of porokeratosis. American journal of human genetics, 111:896-912, 2024

13. Ito Y, Marouf A, Kogure Y, Koya J, Liévin R, Bruneau J, Tabata M, Saito Y, Shingaki S, Yuasa M, Yamaguchi K, Murakami K, Weil R, Vavasseur M, Andrieu GP, Latiri M, Veleanu L, Dussiot M, André I, Joshi A, Lagresle-Peyrou C, Magerus A, Chaubard S, Lavergne D, Bachy E, Brunet E, Fataccioli V, Brouzes C, Laurent C, de Leval L, Traverse-Glehen A, Bossard C, Parrens M, Meignin V, Philippe L, Rossignol J, Suarez F, Michot JM, Tournilhac O, Damaj G, Lemonnier F, Bôle-Feysot C, Nitschké P, Tesson B, Laurent C, Molina T, Asnafi V, Watatani Y, Chiba K, Okada A, Shiraishi Y, Tsukita S, Izutsu K, Miyoshi H, Ohshima K, Sakata S, Dobashi A, Takeuchi K, Sanada M, Gaulard P, Jaccard A, Ogawa S, Hermine O, Kataoka K, Couronné L. Comprehensive Genetic Profiling Reveals Frequent Alterations of Driver Genes on the X Chromosome in Extranodal NK/T-cell Lymphoma. Cancer research, 84:2181-2201, 2024

14. Shimazu Y, Kanda J, Suzuki K, Wada A, Kikuchi T, Ikeda T, Tsukada N, Miwa A, Itagaki M, Kako S, Nishiwaki K, Ota S, Fujiwara SI, Kataoka K, Doki N, Sawa M, Hiramoto N, Nishikawa A, Imai T, Ichinohe T, Kanda Y, Atsuta Y, Kawamura K. The impact of daratumumab pretreatment on multiple myeloma patients undergoing autologous transplantation. Cancer science, 115:2384-2395, 2024

15. Kuwatsuka Y, Ito H, Tabuchi K, Konuma T, Uchida N, Inamoto Y, Inai K, Nishida T, Ikegame K, Eto T, Katayama Y, Kataoka K, Tanaka M, Takahashi S, Fukuda T, Ichinohe T, Kimura F, Kanda J, Atsuta Y, Matsuo K. Trends in allogeneic hematopoietic cell transplantation survival using population-based descriptive epidemiology method: analysis of national transplant registry data. Bone marrow transplantation, 59:1295-1301, 2024

16. Ohwada C, Sakaida E, Takeda Y, Doki N, Igarashi A, Onizuka M, Toyosaki M, Tanaka M, Tachibana T, Kataoka K, Kato J, Fujisawa S, Kato S, Nakasone H, Naganuma K, Saitoh T, Shono K, Hagihara M, Saito T, Usuki K, Mori T, Nakaseko C, Okamoto S, Kanda Y. Survival impact of response within the first year in a multicenter prospective observational study of chronic GVHD in a Japanese cohort. International journal of hematology, 120:347-355, 2024

17. Araki M, Mitsuhashi T, Yatabe Y, Arai T, Yokota H, Okita H, Sakurai M, Tsukada N, Kataoka K, Matsushita H. Simple flow cytometry method using a myeloma panel that easily reveals clonal proliferation of mature B-cells. Clinical chemistry and laboratory medicine, 2024

18. Nishikubo M, Shimomura Y, Nakaya Y, Shinohara A, Uchida N, Takayama N, Kobayashi H, Uehara Y, Ishikawa J, Ishiwata K, Hiramoto N, Nakazawa H, Kataoka K, Kanda J, Nagafuji K, Kozai Y, Matsuhashi Y, Ishimaru F, Kim SW, Fukuda T, Kanda Y, Atsuta Y, Kondo E, Kako S. Haploidentical transplantation with post-transplant cyclophosphamide versus single cord blood transplantation in adults with relapsed/refractory non-Hodgkin lymphoma. Bone marrow transplantation, 59:1735-1743, 2024

19. Kawase S, Sakurai M, Masuda K, Kubota Y, Shindo T, Inokuchi A, Hayashi H, Nakayasu M, Shiozawa Y, Hirai T, Inoue T, Fujii T, Kim H, Koda Y, Kato J, Kataoka K. Salivary gland swelling as a characteristic manifestation of local cytokine release syndrome after anti-CD19 chimeric antigen receptor T cell therapy: A case series. Journal of clinical and experimental hematopathology : JCEH, 64:261-267, 2024

20. Shimomura Y, Kitamura T, Sugita J, Terao T, Satake A, Hirakawa T, Uchida N, Shimabukuro M, Tanaka M, Eto T, Hiramoto N, Kataoka K, Nakamae H, Takase K, Kawakita T, Arai Y, Takeda W, Ishimaru F, Fukuda T, Atsuta Y, Nakasone H, Kanda J. Impact of donor type on the outcomes of acute graft versus host disease to systemic corticosteroid therapy. Bone marrow transplantation, 59:1763-1772, 2024

21. Koya J, Tanigawa T, Mizuno K, Kim H, Ito Y, Yuasa M, Yamaguchi K, Kogure Y, Saito Y, Shingaki S, Tabata M, Murakami K, Chiba K, Okada A, Shiraishi Y, Marouf A, Liévin R, Chaubard S, Jaccard A, Hermine O, de Leval L, Tournilhac O, Damaj G, Gaulard P, Couronné L, Yasui T, Nakashima K, Miyoshi H, Ohshima K, Kataoka K. Modeling NK-cell lymphoma in mice reveals its cell-of-origin and microenvironmental changes and identifies therapeutic targets. Nature communications, 15:9106, 2024

22. Jo T, Inoue K, Ueda T, Iwasaki M, Akahoshi Y, Nishiwaki S, Hatsusawa H, Nishida T, Uchida N, Ito A, Tanaka M, Takada S, Kawakita T, Ota S, Katayama Y, Takahashi S, Onizuka M, Hasegawa Y, Kataoka K, Kanda Y, Fukuda T, Tabuchi K, Atsuta Y, Arai Y. Machine learning evaluation of intensified conditioning on haematopoietic stem cell transplantation in adult acute lymphoblastic leukemia patients. Communications medicine, 4:247, 2024

23. Kubota Y, Sakurai M, Nannya Y, Kogure Y, Shiroshita K, Fujita S, Yamaguchi K, Mizuno K, Kato J, Mori T, Ogawa S, Kataoka K. Post-transplant transient abnormal myelopoiesis evolving from a GATA1 mutant clone in umbilical cord blood. Annals of hematology, 103:5989-5998, 2024

24. Kikuchi T, Wakui M, Katagiri H, Yamaguchi K, Osada E, Murata M, Kataoka K. Multiple myeloma with coagulopathy suspected of being due to paraprotein with lupus anticoagulants activity. Int J Myeloma, 14:1-4, 2024