Single-cell analysis dissects clonal specific chromatin states relevant to pathology and relapse in AML

Acute myeloid leukemia (AML) is a rapidly progressing hematopoietic malignancy, characterized by the accumulation of clonal myeloid stem or progenitor cells arrested in their ability to differentiate into mature blood cells. Although most patients initially respond to chemotherapy, ~75% relapse and death within 5-years.

The t(8;21)(q22;q22) translocation is one of the most frequent genetic alterations in AML, and is typically present in French-American-British (FAB)-M2 subtype.

Despite progresses in the understanding of AML pathophysiology, the molecular pathogenesis and relapse of AML has not yet been completely defined.

Here, we use a new single cell profiling technology called mtscATAC-seq, which allows us to define the epigenomic clonal evolution of AML using endogenous mitochondrial DNA variants as well as the cellular output of each clone, in order to identify putative epigenetic mechanisms of AML pathogenesis and relapse at the single-cell resolution.

Combining with the bioinformatic analysis, we will define the epigenomic clonal evolution of AML hematopoietic stem and progenitor cells and their progenies in patients with AML.