An anti-apoptotic pattern correlates with multidrug resistance in acute myeloid leukemia patients: A comparative study of active caspase-3, cleaved PARPs, Bcl-2, Survivin and MDR1 gene

Abstract

Bone marrow samples of 17 acute myeloid leukemia (AML) patients were analyzed for apoptosis-related markers. The levels of active caspase-3 (aC-3), Bcl-2 and cleaved poly(ADP-ribose) polymerase (cPARP) were measured by flow cytometry and compared with survivin and MDR1 gene expression as defined by reverse transcriptase polymerase chain reaction (RT-PCR). The results showed heterogeneous patterns of intracellular levels of the studied proteins in AML patients: aC-3 (mean 34•6±52•5 U/ml), Bcl-2 (mean 3268•4±2055•2 U/ml), and cPARPs (mean 24•59± 29•97 U/ml). Survivin and MDR1 genes were overexpressed in 9 and 10 patients, respectively. Patients with high levels of survivin mRNA showed significantly lower cPARPs (11•8±14•3 versus 53•9±31•9 U/ml P=0•005) and a tendency towards higher aC-3 (49•3±70•0 versus 18•1±9•9 U/ml), and MDR1 overexpression (7/9 patients versus 3/8 patients), as well as poorer therapeutic response and survival. Our data support the potential relevance of apoptosis-related markers in AML for further understanding the disease; however, the heterogeneity and complexity of molecular interactions warrants further prospective studies. © 2010 Maney Publishing.