Activin A contributes to the definition of a pro-oncogenic bone marrow microenvironment in t(12;21) preleukemia

摘要: The TEL-AML1 fusion gene, generated by the t(12;21) chromosome translocation, arises in a progenitor/stem cell and could induce clonal expansion of persistent preleukemic B-cell clone which, on acquisition secondary alterations, may turn into full-blown leukemia. During infections, deregulated cytokine signaling, including transforming growth factor β (TGF-β), can further accelerate this process creating protumoral bone marrow (BM) microenvironment. Here, we show that activin A, member TGF-β family induced under inflammatory conditions, inhibits proliferation normal progenitor B cells but not TEL-AML1–positive clones, thereby providing selective advantage to latter. Finally, find A BM-derived mesenchymal stromal cell-mediated secretion CXCL12, major chemoattractant BM compartment, contributing shape leukemia-promoting environment. Overall, our findings indicate concert with TGF-β, play an important role creation pro-oncogenic microenvironment provide novel mechanistic insights TEL-AML1-associated leukemogenesis.