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.

急性髓性白血病 (AML) 患者的分类依赖于形态学、细胞遗传学和分子特征。在这里，我们建立了一种新的基于流式细胞术的免疫表型分层，表明 AML 原始细胞在分化的特定阶段被阻断，其中正常骨髓生成​​的特征得以保留。在 2087 名和 1209 名 AML 患者的两个独立队列中确定了基于 CD34、CD117、CD13、CD33、MPO 和 HLA-DR 表达的六个阶段的白血病分化停止类别。造血干细胞/多能祖细胞样 AMLs 表现出低增殖率、inv(3) 或RUNX1突变、高白血病干细胞频率以及不良结果，而粒细胞 - 单核细胞祖细胞样 AMLs 具有CEBPA突变，RUNX1-RUNX1T1或CBFB-MYH11易位，白血病干细胞频率更低，化学敏感性更高，结果更好。NPM1突变与白血病停滞的大多数成熟阶段相关，与粒细胞祖细胞样 AML 中的TET2或IDH突变或单核细胞祖细胞样 AML 中的DNMT3A突变相关。总体而言，我们证明 AML 在与 AML 遗传病变、临床表现、干细胞特性、化学敏感性、对治疗的反应和结果显着相关的骨髓分化（SLA 分类）的特定阶段被阻止。