Classifications of acute myeloid leukemia (AML) patients rely on morphologic, cytogenetic, and molecular features. Here we have established a novel flow cytometry-based immunophenotypic stratification showing that AML blasts are blocked at specific stages of differentiation where features of normal myelopoiesis are preserved. Six stages of leukemia differentiation-arrest categories based on CD34, CD117, CD13, CD33, MPO, and HLA-DR expression were identified in two independent cohorts of 2087 and 1209 AML patients. Hematopoietic stem cell/multipotent progenitor-like AMLs display low proliferation rate, inv(3) or RUNX1 mutations, and high leukemic stem cell frequency as well as poor outcome, whereas granulocyte–monocyte progenitor-like AMLs have CEBPA mutations, RUNX1-RUNX1T1 or CBFB-MYH11 translocations, lower leukemic stem cell frequency, higher chemosensitivity, and better outcome. NPM1 mutations correlate with most mature stages of leukemia arrest together with TET2 or IDH mutations in granulocyte progenitors-like AML or with DNMT3A mutations in monocyte progenitors-like AML. Overall, we demonstrate that AML is arrested at specific stages of myeloid differentiation (SLA classification) that significantly correlate with AML genetic lesions, clinical presentation, stem cell properties, chemosensitivity, response to therapy, and outcome.
急性髓系白血病（AML）患者的分类依赖于形态学、细胞遗传学和分子特征。本研究建立了一种基于流式细胞术的新型免疫表型分层方法，显示AML原始细胞阻滞在特定分化阶段，并保留了正常髓系分化特征。通过CD34、CD117、CD13、CD33、MPO和HLA-DR的表达分析，我们在两个独立队列（分别为2087例和1209例AML患者）中确定了六类白血病分化阻滞阶段。造血干细胞/多能祖细胞样AML表现为低增殖率、inv(3)或RUNX1突变、高白血病干细胞频率及不良预后；而粒-单核祖细胞样AML则具有CEBPA突变、RUNX1-RUNX1T1或CBFB-MYH11易位、较低的白血病干细胞频率、更高的化疗敏感性及较好预后。NPM1突变与最成熟阶段的白血病阻滞相关：在粒细胞祖细胞样AML中常伴随TET2或IDH突变，在单核细胞祖细胞样AML中则多与DNMT3A突变共存。总体而言，我们证明AML被阻滞在髓系分化的特定阶段（SLA分类），该分类与AML遗传学异常、临床表现、干细胞特性、化疗敏感性、治疗反应及预后显著相关。
肿瘤(癌症)患者之家