Low-Expression of UBE2O in Bone Marrow Mesenchymal Stromal Cells Promotes Acute Myeloid Leukemia Progression

Bone marrow mesenchymal stromal cells (BM-MSCs), important components of BM niche, have been implicated in the pathogenesis of acute myeloid leukemia (AML). In order to investigate the mechanism underlying the crosstalk between MSCs and leukemia cells, our study demonstrated functional differences between MSCs originating from normal and AML mice. We found that AML mice derived MSCs showed higher proliferative viability and reduced apoptosis compared to control. According to RNA-seq results of MSCs, ubiquitin-conjugating enzyme E2O (UBE2O) was proved to be down-regulated in AML derived MSCs and over-expression of UBE2O in MSCs using retrovirus could inhibit MSCs proliferation via inactivation of NF-kB signaling pathway while showed no effect on apoptosis. After co-cultured with AML cells in vitro, MSCs with UBE2O over-expression could inhibit the proliferation of leukemia cells and promote their apoptosis via direct contact. Additionally, the leukemia burden was reduced when leukemia cells were injected into mice by tail vein with UBE2O-overexpressed MSCs and the overall survival of AML mice was prolonged compared to control mice injected with leukemia cells and control MSCs. Subcutaneous formation assay also confirmed that UBE2O-overexpressed MSCs could inhibit tumor formation induced by AML cells. In conclusion, AML cells remodeled bone marrow microenvironment to facilitate low expression of UBE2O in MSCs, leading to promotion of MSCs proliferation, which in turn enhanced AML progression. Over-expression of UBE2O in MSCs not only inhibit the proliferation of MSCs, but also inhibit the progression of AML.

No relevant conflicts of interest to declare.