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

摘要

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.