Promyelocytic Leukemia-specific PML-Retinoic Acid α Receptor Fusion Protein Interferes with Erythroid Differentiation of Human Erythroleukemia K562 Cells¹

Acute promyelocytic leukemia (APL) is characterized by a t(15;17) chromosomal translocation with breakpoints within the retinoic acid α receptor (RARα) gene on 17 and the PML gene, which encodes a putative transcription factor, on 15. A PML-RARα fusion protein is formed as a consequence of the translocation. We show here that expression of the PML-RARα protein in K562 erythroleukemia cells results in a reduced expression of erythroid differentiation markers and a reduced sensitivity to the erythroid differentiative action of heme. Overexpression of RARα, but not of PML, elicited a similar inhibition of K562 erythroid differentiation. These findings indicate that overexpression of either RARα or PML/RARα interferes with erythroid differentiation and support the hypothesis that RARα is involved in the regulation of normal hematopoiesis and alteration of the RARα signaling by PML/RARα is implicated in the promyelocytic leukemogenesis.