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

✍ Scribed by Guosheng Jiang; Ami Albihn; Tianhua Tang; Zhigang Tian; Marie Henriksson

• Publisher: Elsevier Science
• Year: 2008
• Tongue: English
• Weight: 987 KB
• Volume: 32
• Category: Article
• ISSN: 0145-2126
• DOI: 10.1016/j.leukres.2007.06.021

✦ Synopsis

Acute promyelocytic leukemia (APL) is highly malignant and frequently expresses the PML-RAR␣ (promyelocytic leukemia-retinoic acid receptor-␣) 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-RAR␣-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.