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<p>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 (<i>TET3</i>, <i>HLA-C</i>, <i>NRAS</i>, and <i>KLF2</i>). Then, we classified nTFHL cases into four molecular subgroups by major driver alterations. TR-I (+) and TR-I (−) were characterized by <i>TET2</i> and/or <i>RHOA</i> mutations with and without <i>IDH2</i> mutations; AC53 by <i>TP53</i> and/or <i>CDKN2A</i> 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 <i>TP53</i> and/or <i>CDKN2A</i> 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 <i>TP53</i> and/or <i>CDKN2A</i> alterations and the presence of driver alterations, demonstrating the clinical relevance of molecular classification in nTFHL.</p>

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

  • 期刊论文

  • 发表日期：

    2025年5月2日

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  • Yuta Ito,
  • Joji Shimono,
  • Keisuke Kawamoto,
  • Kanako C. Hatanaka,
  • Yasunori Kogure,
  • Mariko Tabata,
  • Yuki Saito,
  • Kota Mizuno,
  • Sara Horie,
  • Yosuke Mizukami,
  • Junji Koya,
  • Koichi Murakami,
  • Takanori Teshima,
  • Yutaka Hatanaka,
  • Kenichi Chiba,
  • Ai Okada,
  • Yuichi Shiraishi,
  • Hiroaki Miyoshi,
  • Yoshihiro Matsuno,
  • Koichi Ohshima,
  • Keisuke Kataoka,
  • Masao Nakagawa

摘要

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.