Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

LYMPHOMA

TP53 and CDKN2A alterations define a poor prognostic subgroup in patients with nodal T follicular helper cell lymphoma

Leukemia volume 39, pages 1723–1734 (2025)Cite this article

Subjects

Abstract

Nodal T follicular helper cell lymphoma (nTFHL) exhibits unique immunophenotypes and somatic alterations, while the prognostic value of these alterations remains unclear. By analyzing 173 nTFHL cases, we identified 36 driver genes, including 4 novel ones (TET3, HLA-C, NRAS, and KLF2). Then, we classified nTFHL cases into four molecular subgroups by major driver alterations. TR-I (+) and TR-I (−) were characterized by TET2 and/or RHOA mutations with and without IDH2 mutations; AC53 by TP53 and/or CDKN2A alterations and aneuploidy; and NSD with no subgroup-defining alterations (namely without any of the above alterations). AC53 exhibited the worst survival, while NSD, particularly those lacking driver alterations, showed the best prognosis. nTFHL had a better prognosis than peripheral T-cell lymphoma, not otherwise specified, when TP53 and/or CDKN2A alterations were absent. Multivariable analyses showed that AC53, the presence of driver alterations, and international prognostic index high-risk were independently associated with worse survival. Finally, we developed a simple prognostic index (mTFHL-PI), which classified patients into three risk categories with a median OS of 181, 67, and 20 months, respectively. Our study identifies novel prognostic factors, namely TP53 and/or CDKN2A alterations and the presence of driver alterations, demonstrating the clinical relevance of molecular classification in nTFHL.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The entire landscape of genetic alterations in nTFHL.
Fig. 2: Molecular subgroups characterized by distinct genetic alterations in nTFHL.
Fig. 3: Differences in pathological and clinical features across molecular subgroups in nTFHL.
Fig. 4: Impact of the presence of driver alterations in the NSD subgroup.
Fig. 5: Association between EBV infection and clinical factors in nTFHL.
Fig. 6: Comparison between nTFHL-AI, nTFHL-NOS, and PTCL-NOS.
Fig. 7: Multivariable analysis of genetic alterations and clinical factors in nTFHL.

Similar content being viewed by others

Data availability

The data generated in this study are available upon request from the corresponding author.

References

  1. Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, IBdO Araujo, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36:1720–48.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Campo E, Jaffe ES, Cook JR, Quintanilla-Martinez L, Swerdlow SH, Anderson KC, et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. Blood. 2022;140:1229–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. de Leval L, Alizadeh AA, Bergsagel PL, Campo E, Davies A, Dogan A, et al. Genomic profiling for clinical decision making in lymphoid neoplasms. Blood. 2022;140:2193–227.

    Article  PubMed  PubMed Central  Google Scholar 

  4. de Leval L, Rickman DS, Thielen C, Reynies A, Huang YL, Delsol G, et al. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood. 2007;109:4952–63.

    Article  PubMed  Google Scholar 

  5. Mourad N, Mounier N, Brière J, Raffoux E, Delmer A, Feller A, et al. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials. Blood. 2008;111:4463–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tokunaga T, Shimada K, Yamamoto K, Chihara D, Ichihashi T, Oshima R, et al. Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma: a multicenter cooperative study in Japan. Blood. 2012;119:2837–43.

    Article  CAS  PubMed  Google Scholar 

  7. Laurence de L, Marie P, Fabien Le B, Jean-Philippe J, Virginie F, Antoine M, et al. Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets. Haematologica. 2015;100:e361–e364.

    Article  Google Scholar 

  8. Couronne L, Bastard C, Bernard OA. TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med. 2012;366:95–96.

    Article  CAS  PubMed  Google Scholar 

  9. Lemonnier F, Couronné L, Parrens M, Jaïs JP, Travert M, Lamant L, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012;120:1466–9.

    Article  CAS  PubMed  Google Scholar 

  10. Lewis NE, Petrova-Drus K, Huet S, Epstein-Peterson ZD, Gao Q, Sigler AE, et al. Clonal hematopoiesis in angioimmunoblastic T-cell lymphoma with divergent evolution to myeloid neoplasms. Blood Adv. 2020;4:2261–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46:171–5.

    Article  CAS  PubMed  Google Scholar 

  12. Yoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S, et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46:371–5.

    Article  CAS  PubMed  Google Scholar 

  13. Palomero T, Couronné L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014;46:166–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Odejide O, Weigert O, Lane AA, Toscano D, Lunning MA, Kopp N, et al. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood. 2014;123:1293–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cairns RA, Iqbal J, Lemonnier F, Kucuk C, de Leval L, Jais J-P, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012;119:1901–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang C, McKeithan TW, Gong Q, Zhang W, Bouska A, Rosenwald A, et al. IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma. Blood. 2015;126:1741–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Vallois D, Dobay MPD, Morin RD, Lemonnier F, Missiaglia E, Juilland M, et al. Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell–derived lymphomas. Blood. 2016;128:1490–502.

    Article  CAS  PubMed  Google Scholar 

  18. Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124–30.

    Article  PubMed  Google Scholar 

  19. Horwitz S, O’Connor OA, Pro B, Trümper L, Iyer S, Advani R, et al. The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma. Ann Oncol. 2022;33:288–98.

    Article  CAS  PubMed  Google Scholar 

  20. Sabattini E, Pizzi M, Tabanelli V, Baldin P, Sacchetti CS, Agostinelli C, et al. CD30 expression in peripheral T-cell lymphomas. Haematologica. 2013;98:e81–82.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Schmitz N, Lenz G, Stelljes M. Allogeneic hematopoietic stem cell transplantation for T-cell lymphomas. Blood. 2018;132:245–53.

    Article  CAS  PubMed  Google Scholar 

  22. Schmitz N, Truemper L, Bouabdallah K, Ziepert M, Leclerc M, Cartron G, et al. A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL. Blood. 2021;137:2646–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Basha BM, Bryant SC, Rech KL, Feldman AL, Vrana JA, Shi M, et al. Application of a 5 marker panel to the routine diagnosis of peripheral T-cell lymphoma with T-follicular helper phenotype. American J Surgical Pathol. 2019;43:1282–90.

    Article  Google Scholar 

  24. Watatani Y, Sato Y, Miyoshi H, Sakamoto K, Nishida K, Gion Y, et al. Molecular heterogeneity in peripheral T-cell lymphoma, not otherwise specified revealed by comprehensive genetic profiling. Leukemia. 2019;33:2867–83.

    Article  CAS  PubMed  Google Scholar 

  25. Fukuhara S, Oshikawa-Kumade Y, Kogure Y, Shingaki S, Kariyazono H, Kikukawa Y, et al. Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies. Cancer Sci. 2022;113:2763–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Martincorena I, Raine KM, Gerstung M, Dawson KJ, Haase K, Van Loo P, et al. Universal patterns of selection in cancer and somatic tissues. Cell. 2017;171:1029–1041.e1021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dobay MP, Lemonnier F, Missiaglia E, Bastard C, Vallois D, Jais JP, et al. Integrative clinicopathological and molecular analyses of angioimmunoblastic T-cell lymphoma and other nodal lymphomas of follicular helper T-cell origin. Haematologica. 2017;102:e148–e151.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ko M, An J, Pastor WA, Koralov SB, Rajewsky K, Rao A. TET proteins and 5-methylcytosine oxidation in hematological cancers. Immunol Rev. 2015;263:6–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, et al. A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications. Cancer Cell. 2020;37:551–568.e514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bonfiglio F, Bruscaggin A, Guidetti F, Terzi di Bergamo L, Faderl M, Spina V, et al. Genetic and phenotypic attributes of splenic marginal zone lymphoma. Blood. 2022;139:732–47.

    Article  CAS  PubMed  Google Scholar 

  31. Kataoka K, Iwanaga M, Yasunaga J-i, Nagata Y, Kitanaka A, Kameda T, et al. Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma. Blood. 2018;131:215–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Heavican TB, Bouska A, Yu J, Lone W, Amador C, Gong Q, et al. Genetic drivers of oncogenic pathways in molecular subgroups of peripheral T-cell lymphoma. Blood. 2019;133:1664–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yoon SE, Cho J, Kim YJ, Ko YH, Park WY, Kim SJ, et al. Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas. Exp Hematol Oncol. 2021;10:33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Johnson WT, Ganesan N, Epstein-Peterson ZD, Moskowitz AJ, Stuver RN, Maccaro CR, et al. TP53 mutations identify high-risk events for peripheral T-cell lymphoma treated with CHOP-based chemotherapy. Blood Adv. 2023.

  35. Cortes JR, Ambesi-Impiombato A, Couronné L, Quinn SA, Kim CS, da Silva Almeida AC, et al. RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis. Cancer Cell. 2018;33:259–273.e257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ng SY, Brown L, Stevenson K, deSouza T, Aster JC, Louissaint A, et al. RhoA G17V is sufficient to induce autoimmunity and promotes T-cell lymphomagenesis in mice. Blood. 2018;132:935–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Leca J, Lemonnier F, Meydan C, Foox J, El Ghamrasni S, Mboumba DL, et al. IDH2 and TET2 mutations synergize to modulate T Follicular Helper cell functional interaction with the AITL microenvironment. Cancer Cell. 2023;41:323–339.e310.

    Article  CAS  PubMed  Google Scholar 

  38. O’Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, et al. Belinostat in patients with relapsed or refractory peripheral t-cell lymphoma: results of the pivotal phase II BELIEF (CLN-19) Study. J Clin Oncol. 2015;33:2492–9.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Shi Y, Dong M, Hong X, Zhang W, Feng J, Zhu J, et al. Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015;26:1766–71.

    Article  CAS  PubMed  Google Scholar 

  40. Tan D, Phipps C, Hwang WY, Tan SY, Yeap CH, Chan YH, et al. Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial. Lancet Haematol. 2015;2:e326–333.

    Article  PubMed  Google Scholar 

  41. Ghione P, Faruque P, Mehta-Shah N, Seshan V, Ozkaya N, Bhaskar S, et al. T follicular helper phenotype predicts response to histone deacetylase inhibitors in relapsed/refractory peripheral T-cell lymphoma. Blood Adv. 2020;4:4640–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Falchi L, Ma H, Klein S, Lue JK, Montanari F, Marchi E, et al. Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study. Blood. 2021;137:2161–70.

    Article  CAS  PubMed  Google Scholar 

  43. Ruan J, Moskowitz A, Mehta-Shah N, Sokol L, Chen Z, Kotlov N, et al. Multicenter phase 2 study of oral azacitidine (CC-486) plus CHOP as initial treatment for PTCL. Blood. 2023;141:2194–205.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Rai S, Kim WS, Ando K, Choi I, Izutsu K, Tsukamoto N, et al. Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results. Haematologica. 2023;108:811–21.

    Article  CAS  PubMed  Google Scholar 

  45. Camus V, Thieblemont C, Gaulard P, Cheminant M, Casasnovas RO, Ysebaert L, et al. Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial. J Clin Oncol. 2024;42:1612–8.

  46. Chen Z, John Wherry E. T cell responses in patients with COVID-19. Nature Rev Immunol. 2020;20:529–36.

    Article  CAS  Google Scholar 

  47. Zheng L, Qin S, Si W, Wang A, Xing B, Gao R, et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science. 2021;374:abe6474.

    Article  PubMed  Google Scholar 

  48. Rosetti F, Madera-Salcedo IK, Rodríguez-Rodríguez N, Crispín JC. Regulation of activated T cell survival in rheumatic autoimmune diseases. Nature Rev Rheumatol. 2022;18:232–44.

    Article  CAS  Google Scholar 

  49. Young LS, Rickinson AB. Epstein–Barr virus: 40 years on. Nature Rev Cancer. 2004;4:757–68.

    Article  CAS  PubMed  Google Scholar 

  50. Fujisawa M, Nguyen TB, Abe Y, Suehara Y, Fukumoto K, Suma S, et al. Clonal germinal center B cells function as a niche for T-cell lymphoma. Blood. 2022;140:1937–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Meeuwes FO, Brink M, van der Poel MWM, Kersten MJ, Wondergem M, Mutsaers P, et al. Impact of rituximab on treatment outcomes of patients with angioimmunoblastic T-cell lymphoma; a population-based analysis. Eur J Cancer. 2022;176:100–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the hematologists and pathologists who were involved in North Japan Hematology Study Group (Supplementary Appendix) for patient care and Y.Hokama, F.Ueki, and Yoshiko Ito for technical assistance. The supercomputing resources were provided by the Human Genome Center, the Institute of Medical Science, The University of Tokyo.

Funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (JP21H05051), Japan Science and Technology Agency Moonshot R&D Program (JPMJMS2022), and Takeda Science Foundation to K.Kataoka, and by JSPS KAKENHI (JP21H02775) to M.N.

Author information

Author notes

  1. These authors contributed equally: Yuta Ito, Joji Shimono, Keisuke Kawamoto.

Authors and Affiliations

  1. Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan

    Yuta Ito, Yasunori Kogure, Mariko Tabata, Yuki Saito, Kota Mizuno, Sara Horie, Yosuke Mizukami, Junji Koya, Koichi Murakami & Keisuke Kataoka

  2. Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Yuta Ito

  3. Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan

    Joji Shimono, Takanori Teshima & Masao Nakagawa

  4. Department of Pathology, Kurume University School of Medicine, Kurume, Japan

    Keisuke Kawamoto, Hiroaki Miyoshi & Koichi Ohshima

  5. Institute of Pathology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany

    Keisuke Kawamoto

  6. Center for Development of Advanced Diagnostics, Hokkaido University Hospital, Sapporo, Japan

    Kanako C. Hatanaka

  7. Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Mariko Tabata

  8. Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan

    Yuki Saito, Sara Horie & Yosuke Mizukami

  9. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Kota Mizuno, Koichi Murakami & Keisuke Kataoka

  10. Research Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo, Japan

    Yutaka Hatanaka

  11. Division of Genome Analysis Platform Development, National Cancer Center Research Institute, Tokyo, Japan

    Kenichi Chiba, Ai Okada & Yuichi Shiraishi

  12. Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan

    Yoshihiro Matsuno

Authors
  1. Yuta Ito
    View author publications

    Search author on:PubMed Google Scholar

  2. Joji Shimono
    View author publications

    Search author on:PubMed Google Scholar

  3. Keisuke Kawamoto
    View author publications

    Search author on:PubMed Google Scholar

  4. Kanako C. Hatanaka
    View author publications

    Search author on:PubMed Google Scholar

  5. Yasunori Kogure
    View author publications

    Search author on:PubMed Google Scholar

  6. Mariko Tabata
    View author publications

    Search author on:PubMed Google Scholar

  7. Yuki Saito
    View author publications

    Search author on:PubMed Google Scholar

  8. Kota Mizuno
    View author publications

    Search author on:PubMed Google Scholar

  9. Sara Horie
    View author publications

    Search author on:PubMed Google Scholar

  10. Yosuke Mizukami
    View author publications

    Search author on:PubMed Google Scholar

  11. Junji Koya
    View author publications

    Search author on:PubMed Google Scholar

  12. Koichi Murakami
    View author publications

    Search author on:PubMed Google Scholar

  13. Takanori Teshima
    View author publications

    Search author on:PubMed Google Scholar

  14. Yutaka Hatanaka
    View author publications

    Search author on:PubMed Google Scholar

  15. Kenichi Chiba
    View author publications

    Search author on:PubMed Google Scholar

  16. Ai Okada
    View author publications

    Search author on:PubMed Google Scholar

  17. Yuichi Shiraishi
    View author publications

    Search author on:PubMed Google Scholar

  18. Hiroaki Miyoshi
    View author publications

    Search author on:PubMed Google Scholar

  19. Yoshihiro Matsuno
    View author publications

    Search author on:PubMed Google Scholar

  20. Koichi Ohshima
    View author publications

    Search author on:PubMed Google Scholar

  21. Keisuke Kataoka
    View author publications

    Search author on:PubMed Google Scholar

  22. Masao Nakagawa
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Y.I.: Formal analysis, investigation, data curation, writing – original draft, writing – review and editing, visualization. J.S.: Investigation, data curation, resources, writing – review and editing. K.Kawamoto: Investigation, resources, writing – original draft, writing – review and editing. K.C.H.: Investigation, resources, writing – review and editing. Y.K.: Formal analysis, writing – original draft, writing – review and editing. M.T.: Formal analysis, writing – review and editing. Y.Saito.: Formal analysis, writing – review and editing. K.Mizuno: Formal analysis, writing – review and editing. S.H.: Formal analysis, writing – review and editing. Y.Mizukami: Formal analysis, writing – review and editing. J.K.: Investigation, writing – review and editing. K.Murakami: Investigation, writing – review and editing. T.T.: Investigation, resources, writing – review and editing. Y.H.: Investigation, resources, writing – review and editing. K.C.: Software, writing – review and editing. A.O.: Software, writing – review and editing. Y.Shiraishi: Software, writing – review and editing. H.M.: Investigation, resources, writing – original draft, writing – review and editing. Y.Matsuno: Investigation, resources, writing – review and editing. K.O.: Conceptualization, investigation, resources, writing – original draft, writing – review and editing, project administration. K.Kataoka: Conceptualization, formal analysis, writing – original draft, writing–review and editing, project administration, funding acquisition. M.N.: Conceptualization, resources, data curation, writing – original draft, writing – review and editing, project administration, funding acquisition.

Corresponding authors

Correspondence to Koichi Ohshima, Keisuke Kataoka or Masao Nakagawa.

Ethics declarations

Competing interests

K.C.H. has received research funding from NEC Corporation, Eli Lilly, and SEKISUI CHEMICAL. Y.K. has received honoraria from Kyowa Kirin, Nippon Shinyaku, Daiichi Sankyo, and Takeda Pharmaceutical. J.K. has received honoraria from TOMY DIGITAL BIOLOGY, Scrum, and Eisai. T.T. has received honoraria from Astellas Pharma, AstraZeneca, Kyowa-Kirin, SymBio Pharmaceuticals, Sumitomo Pharma, Nippon Shinyaku, Novartis, Janssen Pharmaceutical, and Bristol-Myers Squibb; has received research grants from Asahi Kasei Pharma, Eisai, Ono Pharmaceutical, Kyowa-Kirin, Shionogi, Sumitomo Pharma, Chugai Pharmaceutical, and Nippon Shinyaku; and has received research funding from Astellas Pharma, Otsuka Pharmaceutical, LUCA Science, and Priothera SAS. Y.H. has received honoraria from Eli Lilly, Daiichi Sankyo, AstraZeneca, Merck, Novartis, and Merck Sharp & Dohme; has received research funding from NEC Corporation, Eli Lilly, Shionogi, Daiichi Sankyo, and Sysmex; and has received consultancy fee from NEC Corporation. K.Kataoka has received honoraria from Ono Pharmaceutical, Eisai, Astellas Pharma, Novartis, Chugai Pharmaceutical, AstraZeneca, Sumitomo Pharma, Kyowa Kirin, Janssen Pharmaceutical, Takeda Pharmaceutical, Otsuka Pharmaceutical, SymBio Pharmaceuticals, Bristol Myers Squibb, Pfizer, Nippon Shinyaku, Daiichi Sankyo, Alexion Pharmaceuticals, AbbVie, Meiji Seika Pharma, Sanofi, Sysmex, Mundipharma, Incyte Corporation, and Kyorin Pharmaceutical; has received research funding from Asahi Kasei Pharma, Eisai, Otsuka Pharmaceutical, Ono Pharmaceutical, Kyowa Kirin, Shionogi, Takeda Pharmaceutical, Sumitomo Dainippon Pharma, Chugai Pharmaceutical, Teijin Pharma, Japan Blood Products Organization, Mochida Pharmaceutical, JCR Pharmaceuticals, Nippon Shinyaku, Chordia Therapeutics, and Meiji Seika Pharma; holds individual stocks in Asahi Genomics; and has a patent for Genetic alterations as a biomarker in T-cell lymphomas licensed to Kyoto University and PD-L1 abnormalities as a predictive biomarker for immune checkpoint blockade therapy licensed to Kyoto University. M.N. has received honoraria from Takeda Pharmaceutical, Meiji Seika Pharma, AstraZeneca, and Mundipharma; and has received research funding from Takeda Pharmaceutical and AbbVie. All remaining authors have declared no conflicts of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ito, Y., Shimono, J., Kawamoto, K. et al. TP53 and CDKN2A alterations define a poor prognostic subgroup in patients with nodal T follicular helper cell lymphoma. Leukemia 39, 1723–1734 (2025). https://doi.org/10.1038/s41375-025-02631-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41375-025-02631-5

This article is cited by

Search

Advanced search

Quick links