Scholarlink

<p>The inclusion of nine myelodysplasia-related gene (MRG) mutations (<i>ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2</i>) as adverse risk factors in the ELN risk classification has reshaped classification in acute myeloid leukemia (AML). AML with <i>FLT3</i>-ITD mutations and co-occurring MRG alterations is now classified to the ELN adverse risk group although supporting evidence remains limited. Among 4,078 patients with AML with available molecular information included in the HARMONY platform, 862 harbored <i>FLT3</i>-ITD mutations and underwent intensive chemotherapy. Of these, 171 (20%) exhibited co-occurring MRG mutations at diagnosis. In this cohort, MRGs were not independently associated with relapse-free survival (RFS) or overall survival (OS). In the <i>FLT3</i>-ITD/<i>NPM1</i> co-mutated subgroup, MRG mutations were rare (9%) and showed no prognostic impact. Conversely, in <i>FLT3-</i>ITD<i>/NPM1</i> wildtype AML, MRG mutations were predictive of shorter RFS (HR 1.37, 95%CI 1.01 – 1.88, <i>p</i> = 0.046) and OS (HR 1.34, 95%CI 1.02–1.74, <i>p</i> = 0.032) in multivariable analysis with survival times comparable to the ELN adverse risk category. The allelic ratio of <i>FLT3</i>-ITD did not further stratify OS and RFS in this subgroup. These findings suggest that the prognostic relevance of MRG mutations in <i>FLT3</i>-ITD AML is modulated by <i>NPM1</i> co-mutational status and mirror findings in AML lacking <i>FLT3</i>-ITD.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Prognostic impact of myelodysplasia-related gene mutations in FLT3-ITD-mutated acute myeloid leukemia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月9日

查看全文
  • Rabea Mecklenbrauck,
  • Angela Villaverde Ramiro,
  • Eric Sträng,
  • Razif Gabdoulline,
  • Javier Martinez Elicegui,
  • Marta Sobas,
  • Lisa Pleyer,
  • Amin Turki,
  • Maria Teresa Voso,
  • Axel Benner,
  • Alberto Hernández-Sánchez,
  • Jesse M. Tettero,
  • Laura Tur Gimenez,
  • Klaus H. Metzeler,
  • Guadalupe Oñate,
  • Sören Lehmann,
  • Brian JP Huntly,
  • Ian Thomas,
  • Felicitas R. Thol,
  • Florian H. Heidel,
  • Peter JM Valk,
  • Konstanze Döhner,
  • Torsten Haferlach,
  • Kenneth I. Mills,
  • Hartmut Döhner,
  • Gastone Castellani,
  • Gert J. Ossenkoppele,
  • Jesus María Hernández-Rivas,
  • Lars Bullinger,
  • Michael Heuser

摘要

The inclusion of nine myelodysplasia-related gene (MRG) mutations (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2) as adverse risk factors in the ELN risk classification has reshaped classification in acute myeloid leukemia (AML). AML with FLT3-ITD mutations and co-occurring MRG alterations is now classified to the ELN adverse risk group although supporting evidence remains limited. Among 4,078 patients with AML with available molecular information included in the HARMONY platform, 862 harbored FLT3-ITD mutations and underwent intensive chemotherapy. Of these, 171 (20%) exhibited co-occurring MRG mutations at diagnosis. In this cohort, MRGs were not independently associated with relapse-free survival (RFS) or overall survival (OS). In the FLT3-ITD/NPM1 co-mutated subgroup, MRG mutations were rare (9%) and showed no prognostic impact. Conversely, in FLT3-ITD/NPM1 wildtype AML, MRG mutations were predictive of shorter RFS (HR 1.37, 95%CI 1.01 – 1.88, p = 0.046) and OS (HR 1.34, 95%CI 1.02–1.74, p = 0.032) in multivariable analysis with survival times comparable to the ELN adverse risk category. The allelic ratio of FLT3-ITD did not further stratify OS and RFS in this subgroup. These findings suggest that the prognostic relevance of MRG mutations in FLT3-ITD AML is modulated by NPM1 co-mutational status and mirror findings in AML lacking FLT3-ITD.