Role of Myc in differentiation and apoptosis in HL60 cells after exposure to arsenic trioxide or all-trans retinoic acid

Abstract Acute promyelocytic leukemia (APL) is highly malignant and frequently expresses the PML-RARα (promyelocytic leukemia-retinoic acid receptor-α) fusion protein. This fusion protein is targeted by all-trans retinoic acid (ATRA) and arsenic trioxide (As 2 O 3 ), presently used in APL therapy. We have evaluated effects of ATRA and As 2 O 3 treatment in PML-RARα-negative HL60 promyelocytic leukemia cells, harboring amplified c-myc . Characterization of expression and activity of c-Myc and its target genes hTERT ( human telomerase reverse transcriptase ) and CAD ( carbamoyltransferase-dihydroorotase ) revealed marked down-regulation in response to ATRA, but not As 2 O 3 . We suggest that blockage of terminal differentiation upon As 2 O 3 treatment may be mediated through c-Myc.