Improving leukemic CD34+/CD38−blasts characterization with single-cell transcriptome sequencing

SUMMARY / ABSTRACT Acute myeloid leukemia (AML) is a particularly aggressive blood cancer that is difficult to treat because of the incomplete eradication of rare blast cells that possess self-renewal and leukemia-initiating properties. To characterize resistant blasts, we analyzed for the first time the transcriptomes of individual CD3 4+ /CD38 − blasts by single-cell mRNA sequencing of 359 CD33 + /CD34 + /CD38 −/+ sorted cells from two patients with AML and four unaffected individuals. We demonstrated that the captured blasts possess the transcriptomic hallmarks of self-renewal and leukemia-initiating ability. The effects of somatic mutations on the cancer cells are visible at the transcriptional level, and the cellular signaling pathway activity of the blasts is altered, revealing disease-associated gene networks. We also identified a core set of transcription factors that were co-activated in blasts, which suggests a joint transcription program among blasts. Finally, we revealed that leukemogenesis and putative prognostic gene-expression signatures are present at diagnosis in leukemic CD33 + /CD3 4+ /CD38 − cells and can be detected using a single-cell RNA sequencing approach.