Document Detail


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.
MedLine Citation:
PMID:  20557671     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Margarita L Guenova; Gueorgui N Balatzenko; Vessela R Nikolova; Branimir V Spassov; Spiro M Konstantinov
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hematology (Amsterdam, Netherlands)     Volume:  15     ISSN:  1607-8454     ISO Abbreviation:  Hematology     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-18     Completed Date:  2010-10-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9708388     Medline TA:  Hematology     Country:  England    
Other Details:
Languages:  eng     Pagination:  135-43     Citation Subset:  IM    
Affiliation:
Blood Diseases Diagnostic Unit, Laboratory of Haematopathology and Immunology, National Specialised Hospital for Active Treatment of Haematological Diseases, Sofia 1756, Bulgaria. margenova@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Apoptosis / genetics*
Caspase 3 / genetics*,  metabolism
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Female
Gene Expression Regulation, Neoplastic
Humans
Immunophenotyping
Leukemia, Myeloid, Acute / drug therapy,  genetics*,  metabolism,  pathology
Male
Microtubule-Associated Proteins / genetics*,  metabolism
Middle Aged
P-Glycoprotein / genetics*,  metabolism
Poly(ADP-ribose) Polymerases / genetics*,  metabolism
Proto-Oncogene Proteins c-bcl-2 / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/ABCB1 protein, human; 0/BIRC5 protein, human; 0/Microtubule-Associated Proteins; 0/P-Glycoprotein; 0/Proto-Oncogene Proteins c-bcl-2; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspase 3

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