TY - JOUR T1 - Improving leukemic CD34<sup>+</sup>/CD38<sup>−</sup> blasts characterization with single-cell transcriptome sequencing JF - bioRxiv DO - 10.1101/141754 SP - 141754 AU - Ambra Sartori AU - Phil Cheng AU - Emilie Falconnet AU - Pascale Ribaux AU - Jean-Pierre Aubry-Lachainaye AU - Mitchell P. Levesque AU - Stylianos E. Antonarakis AU - Thomas Matthes AU - Christelle Borel Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/31/141754.abstract N2 - 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 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. ER -