RAR-independent RXR signaling induces t(15;17) leukemia cell maturation

Open Access
Publisher Website
Google Scholar
Abstract
Although retinoic acid receptor alpha (RARα) agonists induce the maturation of t(15;17) acute promyelocytic leukemia (APL) cells, drug treatment also selects leukemic blasts expressing PML–RARα fusion proteins with mutated ligand‐binding domains that no longer respond to all‐ trans retinoic acid (ATRA). Here we report a novel RARα‐independent signaling pathway that induces maturation of both ATRA‐sensitive and ATRA‐resistant APL NB4 cells, and does not invoke the ligand‐induced alteration of PML–RARα signaling, stability or compartmentalization. This response involves a cross‐talk between RXR agonists and protein kinase A signaling. Our results indicate the existence of a separate RXR‐dependent maturation pathway that can be activated in the absence of known ligands for RXR heterodimerization partners.