AML 典型突变（CEBPA、FLT3 和 NPM1）可识别独立于 CPSS-Mol 分类的高风险 CMML。
AML typical mutations (CEBPA, FLT3, and NPM1) identify a high-risk CMML independent of CPSS-Mol classification.
发表日期：2024 Oct 10
作者：
Sandra Castaño-Díez, Mònica López-Guerra, Inés Zugasti, Xavier Calvo, Felicitas Isabel Schulz, Alejandro Avendaño, Elvira Mora, Jose Francisco Falantes-González, Gemma Azaceta, Mariam Ibañez, Tzu-Hua Chen-Liang, Cristina Notario Mc Donnell, Neus Amer-Salas, Laura Palomo, Helena Pomares, Jordi Vila, Teresa Bernal Del Castillo, Carlos Jiménez-Vicente, Daniel Esteban, Francesca Guijarro, José Ramón Álamo Moreno, Albert Cortés-Bullich, Víctor Torrecillas-Mayayo, Ana Triguero, Lucía Mont-de Torres, Ester Carcelero, Aina Cardús, Ulrich Germing, Beate Betz, Maria Rozman, Leonor Arenillas, Lurdes Zamora, María Díez-Campelo, Blanca Xicoy, Jordi Esteve, Marina Díaz-Beyá
来源：
Blood Advances
摘要：
通常与急性髓系白血病 (AML) 相关的突变，例如 CEBPA、FLT3、IDH1/2 和 NPM1，在慢性粒单核细胞白血病 (CMML) 中很少发现，并且它们在 CMML 中的预后意义尚未明确。在 127 名 CMML 患者中，我们回顾性分析了诊断 CMML 时进行的骨髓样本分析的下一代测序和 PCR 数据。 7 名患者携带 CEBPA 突变、8 名 FLT3 突变、12 名 IDH1 突变、26 名 IDH2 突变和 11 名 NPM1 突变。携带 CEBPA、FLT3 和/或 NPM1 突变 (mutCFN) 的 CMML 患者更常与骨髓增殖亚型 (MP-CMML)、严重血细胞减少和原始细胞计数升高相关。无论 CPSS-Mol 分类如何，mutCFN CMML 患者的预后都很差，多变量分析将 mutCFN 确定为总生存期的独立标志物。这些 mutCFN CMML 患者的基因谱与 AML 非常相似，具有较高风险的临床特征。我们的发现促使我们建议在 CMML 预后模型中评估这些突变，并在可行的情况下用 AML 型疗法治疗这些患者，包括强化化疗和同种异体干细胞移植，并考虑批准用于 AML 的某些靶向疗法。版权© 2024 美国血液学会。
Mutations commonly associated with acute myeloid leukemia (AML), such as CEBPA, FLT3, IDH1/2 and NPM1 are rarely found in chronic myelomonocytic leukemia (CMML) and their prognostic significance in CMML has not been clearly identified. In 127 CMML patients, we have retrospectively analyzed next-generation sequencing and PCR data from analyses of bone marrow samples performed at diagnosis of CMML. Seven patients harbored CEBPA mutations, eight FLT3 mutations, 12 IDH1 mutations, 26 IDH2 mutations and 11 NPM1 mutations. CMML patients harboring CEBPA, FLT3, and/or NPM1 mutations (mutCFN)were more frequently associated with the myeloproliferative subtype (MP-CMML) , a high prevalence of severe cytopenia, and elevated blast counts. Regardless of their CPSS-Mol classification, mutCFN CMML patients had a poor prognosis, and the multivariate analysis identified mutCFN as an independent marker of overall survival. The genetic profile of these mutCFN CMML patients closely resembled that of AML, with higher-risk clinical characteristics. Our findings lead us to suggest including the assessment of these mutations in CMML prognostic models and treating these patients with AML-type therapies, including intensive chemotherapy and allogeneic stem cell transplantation, whenever feasible, and consider certain targeted therapies approved for use in AML.Copyright © 2024 American Society of Hematology.