Novel Cellular Patterns and Gene Drivers of Relapse in Adult Acute Myelogenous Leukemia

Through the analysis of 20 paired AML specimens procured before and at relapse from therapy we have identified three cellular relapse patterns: i) shift to immaturity; ii) proportional regrowth, and, iii) shift to monocyte-like cells. We traced AML driver mutations back into early HSC/MPP like cells. We identify high confidence genes that are differentially expressed in matched cell types between AML cells at diagnosis versus relapse. We credentialled a subset of these genes via CRISPR-Cas9 screens in ten AML cell lines. Overall, we identify novel patterns and drivers of AML relapse.