Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-ku, Nagoya, 466-8550, Japan.
Int J Hematol. 2024 Nov;120(5):525-527. doi: 10.1007/s12185-024-03848-3. Epub 2024 Oct 1.
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by various molecular abnormalities that significantly impact its pathogenesis and prognosis. Currently, the prognosis of AML patients is stratified on the basis of co-existing chromosomal and genetic abnormalities. AML patients with NPM1 or CEBPA mutations, which are frequently identified in cytogenetically normal AML, are classified in the favorable-risk group, although approximately 40% of patients relapse. Similarly, a clinical high-risk group has been identified among patients with acute promyelocytic leukemia, but the underlying molecular abnormalities remain unclear. FLT3 mutations frequently overlap in these favorable-risk AMLs, including core binding factor AML, and their prognostic impact is still controversial. As such, further risk stratification and treatment optimization based on various molecular abnormalities are warranted to improve the prognosis of favorable-risk AMLs. These molecular abnormalities are also considered therapeutic targets, and targeted therapies have been developed over the years. In recent years, several targeted agents have been approved and demonstrated to improve the prognosis of AML. However, resistance to targeted therapies is also a challenge. This Progress in Hematology features current trends and challenges in favorable-risk AML and FLT3 mutations that are frequently identified in these patients.
急性髓细胞白血病 (AML) 是一种异质性疾病,其特征为各种分子异常,这些异常显著影响其发病机制和预后。目前,AML 患者的预后是基于共存的染色体和遗传异常进行分层的。在核型正常的 AML 中经常发现 NPM1 或 CEBPA 突变的 AML 患者被归类为低危组,但约 40%的患者会复发。同样,在急性早幼粒细胞白血病患者中也确定了临床高危组,但潜在的分子异常仍不清楚。FLT3 突变在这些低危 AML 中经常重叠,包括核心结合因子 AML,其预后影响仍存在争议。因此,有必要基于各种分子异常进一步进行风险分层和治疗优化,以改善低危 AML 的预后。这些分子异常也被认为是治疗靶点,多年来已经开发出了靶向治疗药物。近年来,一些靶向药物已被批准并证明可改善 AML 的预后。然而,对靶向治疗的耐药性也是一个挑战。本期《血液学进展》的特色是目前低危 AML 和这些患者中经常发现的 FLT3 突变的趋势和挑战。