MRC2 expression modulates metabolism in acute myeloid leukemia stem cells

Leukemic stem cells (LSC) are well recognized for their essential roles in acute myeloid leukemia (AML) initiation and relapse. LSC can be distinguished from non-LSC AML cells by the expression of specific cell surface markers, but there is considerable phenotypic heterogeneity among LSC in AML. Here, using primary patient samples, we report that mannose receptor C-type 2 (MRC2) can be used to enrich for LSC across various AML subtypes. When compared to MRC2- AML cells isolated from the same patient samples, MRC2+ leukemic subpopulations show increased in vitro clonogenic capacity, a stemness transcriptomic signature, and enhanced leukemic capacity in mouse xenograft models. Further, we find that MRC2 is functional on AML cells, and enables their robust uptake of collagen, which supports their glycolytic metabolism. In sum these data highlight the use of functional surface markers to distinguish LSC in AML, and how they can yield insight into their unique characteristics.