B-cell precursor acute lymphoblastic leukemia elicits an interferon- α/β response in bone marrow-derived mesenchymal stroma

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can hijack the normal bone marrow microenvironment to create a leukemic niche which facilitates blast cell survival and promotes drug resistance. Bone marrow-derived mesenchymal stromal cells (MSC) mimic this protective environment in ex vivo co-cultures with leukemic cells obtained from children with newly diagnosed BCP-ALL. We examined the potential mechanisms of this protection by RNA sequencing of flow-sorted MSC after co-culture with BCP-ALL cells. Leukemic cells induced an interferon (IFN)-related gene signature in MSC, which was partially dependent on direct cell -cell signaling. The signature was selectively induced by BCP-ALL cells, most profoundly by ETV6-RUNX1 -positive ALL cells, as co-culture of MSC with healthy immune cells did not provoke a similar IFN signature. Leukemic cells and MSC both secreted IFN alpha and IFN 13 , but not IFN gamma . In line, the IFN gene signature was sensitive to blockade of IFN alpha / 13 signaling, but less to that of IFN gamma . The viability of leukemic cells and level of resistance to three chemotherapeutic agents was not affected by interference with IFN signaling using selective IFN alpha / 13 inhibitors or silencing of IFN-related genes. Taken together, our data suggest that the leukemia-induced expression of IFN alpha / 13 -related genes by MSC does not support survival of BCP-ALL cells but may serve a different role in the pathobiology of BCP-ALL.