Promyelocytic leukemia protein in mesenchymal stem cells is essential for leukemia progression

Disease recurrence after therapy, due to the persistence of resistant leukemic cells, represents a fundamental problem in the treatment of leukemia. Elucidating the mechanisms responsible for the maintenance of leukemic cells, before and after treatment, is therefore critical to identify curative modalities. It has become increasingly clear that cell-autonomous mechanisms are not solely responsible for leukemia maintenance. Here, we report a role for Pml in mesenchymal stem cells (MSCs) in supporting leukemic cells of both CML and AML. Mechanistically, we show that Pml regulates pro-inflammatory cytokines within MSCs, and that this function is critical in sustaining CML-KLS and AML ckit+ leukemic cells non-cell autonomously.
Persistence of resistant leukemic cells after therapy is the main cause of relapse. Here, the authors show that mesenchymal stem cells-derived PML is involved in the maintenance of leukemia cells through Cxcl1 and IL6 and that PML inhibition enhances sensitivity to chemotherapy.