Characterizing the immune recognition of chemo-persister blasts in acute myeloid leukemia

Acute myeloid leukemia (AML) is a lethal adult leukemia with high remission rates (~75%) after chemotherapy. Thus, high-risk AML patients often undergo allogeneic hematopoietic cell transplantation (allo-HCT), the only curative treatment option currently available. Allo-HCT relies on the elimination of the blasts that survived chemotherapy by mature immune cells present in the graft, a process known as the graft-versus-leukemia effect. However, around 50% of patients still relapse, demonstrating the immune escape capacity of AML blasts. Recent research revealed that relapse is mediated by a subpopulation of chemo-persister AML blasts that enter a dormant state called diapause in response to chemotherapy. Our study aims to characterize the capacity of these diapause AML cells to evade immune recognition. Accordingly, we first modeled AML chemotherapy by treating cell lines with cytarabine (Ara-C, a common AML chemotherapeutic). We validated that Ara-C induces a diapause gene expression signature and that the transcriptome of treated cells presents key features found in AML blasts from treated patients (notably senescence, autophagy, and dormancy). Next, through functional co-culture assays, we observed that diapause blasts might evade T cells better than regular blasts. We plan to characterize this immune escape capacity in humanized mice and investigate the molecular mechanisms involved.