Bone morphogenetic proteins regulate differentiation of human promyelocytic leukemia cells.

We investigated the role of bone morphogenetic proteins (BMPs) in suppression of all-trans retinoic acid (ATRA)-mediated differentiation of leukemic promyelocytes. In NB4 and HL60 cell lines, BMPs reduced the percentage of differentiated cells, and suppressed PU.1 and C/EBPε gene expression induced by ATRA. BMP and ATRA synergized in the induction of ID genes, causing suppression of differentiation. In primary acute promyelocytic leukemia bone-marrow samples, positive correlation of PML/RARα and negative of RARα with the expression of BMP-4, BMP-6 and ID genes were found. We concluded that BMPs may have oncogenic properties and mediate ATRA resistance by a mechanism that involves ID genes.