Improving Leukemic CD34+/CD38- Blasts Characterization With Single-Cell Transcriptome Sequencing [article]

Ambra Sartori, Phil Cheng, Emilie Falconnet, Pascale Ribaux, Jean-Pierre Aubry-Lachainaye, Mitchell P. Levesque, Stylianos E. Antonarakis, Thomas Matthes, Christelle Borel
2017 bioRxiv   pre-print
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 CD34+/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
more » ... 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+/CD34+/CD38- cells and can be detected using a single-cell RNA sequencing approach.
doi:10.1101/141754 fatcat:6hx7fspxubae7ly43g75b5vi2e