将人类急性髓性白血病（AML）细胞重新编程为诱导性多能干细胞（iPSC）系列可能提供新的可靠的AML遗传模型，但目前受到成功率低和iPSC派生细胞是否类似于其原型的不确定性的限制。在此，我们开发了一种适用于癌细胞的重编程方法，从15名代表AML所有主要遗传群体的患者中生成iPSCs。这些AML-iPSCs保留了遗传准确性，并产生出具有标志性表型白血病特征的可移植造血细胞。关键是，单个细胞转录组学表明，在异种移植后，iPSC派生的白血病忠实地模拟了原始患者相匹配的移植物。移植iPSC派生的白血病，捕获同一患者的一个克隆和亚克隆，使我们能够隔离FLT3-ITD突变对AML表型的贡献。这里报告的结果和资源可以转变AML和其他人类癌症的基础和临床前研究。我们报道了人类AML所有主要遗传群体的患者衍生iPSC模型的生成。这些在体内外表现出AML的表型标志，并提供了人类AML的克隆层次和克隆动力学的信息，并在异种移植后与患者相匹配的原始白血病有惊人的相似之处。请参见Doulatov的相关评论。©2023作者；由美国癌症研究协会出版。

The reprogramming of human acute myeloid leukemia (AML) cells into induced pluripotent stem cell (iPSC) lines could provide new faithful genetic models of AML, but is currently hindered by low success rates and uncertainty about whether iPSC-derived cells resemble their primary counterparts. Here we developed a reprogramming method tailored to cancer cells, with which we generated iPSCs from 15 patients representing all major genetic groups of AML. These AML-iPSCs retain genetic fidelity and produce transplantable hematopoietic cells with hallmark phenotypic leukemic features. Critically, single-cell transcriptomics reveal that, upon xenotransplantation, iPSC-derived leukemias faithfully mimic the primary patient-matched xenografts. Transplantation of iPSC-derived leukemias capturing a clone and subclone from the same patient allowed us to isolate the contribution of a FLT3-ITD mutation to the AML phenotype. The results and resources reported here can transform basic and preclinical cancer research of AML and other human cancers.We report the generation of patient-derived iPSC models of all major genetic groups of human AML. These exhibit phenotypic hallmarks of AML in vitro and in vivo, inform the clonal hierarchy and clonal dynamics of human AML, and exhibit striking similarity to patient-matched primary leukemias upon xenotransplantation. See related commentary by Doulatov.©2023 The Authors; Published by the American Association for Cancer Research.