Molecular and Functional Characterization of Disease-Propagating Stem Cells in Juvenile Myelomonocytic Leukemia [FACS sorted populations]

We report on the characterization of JMML hematopoietic stem and progenitor cells (HSPCs). In order to molecularly characterize these populations we preformed bulk RNA-seq on purified cord blood and JMML HSCs, GMPs, and JMML double positives (+/+). We identified a conserved molecular hierarchy in JMML with high stem cell gene expression in HSCs, high progenitor and cell cycle gene expression in GMPs. We identified enriched gene sets in JMML HSCs vs CB HSCs, and find a number of potential therapeutic targets expressed in JMML.

本研究报道了青少年粒单核细胞白血病（JMML）造血干细胞与祖细胞（HSPCs）的特征表征。为从分子层面解析上述细胞群，我们对纯化后的脐带血、JMML造血干细胞（HSCs）、粒细胞-巨噬细胞祖细胞（GMPs）以及JMML双阳性（+/+）细胞进行了批量RNA测序（bulk RNA-seq）。我们在JMML中鉴定出一条保守的分子层级：造血干细胞内高表达干细胞相关基因，粒细胞-巨噬细胞祖细胞内则高表达祖细胞相关基因与细胞周期相关基因。此外，我们还鉴定出JMML造血干细胞相较于脐带血造血干细胞的富集基因集，并发现了一批在JMML中表达的潜在治疗靶点。