Membrane transport and apoptosis-related proteins in radiation-associated acute myeloid leukemia following the Chornobyl accident.
We report on the results of multidrug-resistance transporters (P-glycoprotein, LRP, and MDR1), and apoptosis-related proteins (Fas, Bcl-2, Bax, p53, and Bcl-X(L)) expression analysis of 56 acute myeloid leukemia (AML) patients by flow cytometry. Of these, there were 21 persons exposed to ionizing radiation due to the Chornobyl accident with radiation-associated and 35 patients with spontaneous AML. Leukemic cells in patients with radiation-associated AML more often overexpressed antiapoptotic protein Bcl-2 (12/21 vs. 6/35, p < 0.005) and less often demonstrated expression of Fas receptor (12/21 vs. 30/35, p < 0.05). Moreover, leukemic cells were simultaneously Fas negative and Bcl-2 positive in 4 out of 21 patients exposed to ionizing radiation but none of spontaneous cases had similar phenotype (p < 0.05). Patients with radiation-associated AML compared to spontaneous cases more often were P-glycoprotein positive (12/20 vs. 9/31, p < 0.05). P-glycoprotein overexpression significantly correlated with the resistance of the disease to chemotherapy in patients with radiation-associated AML (p < 0.05).
Klymenko
Sergiy V
SV
Research Centre for Radiation Medicine, 53 Melnikova, 04050 Kyiv, Ukraine. klymenko_sergiy@yahoo.co.uk
Ilyenko
Iryna N
IN
Golarnik
Natalya A
NA
Maznichenko
Oksana L
OL
Breier
Albert
A
Bazyka
Dimitry A
DA
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D047852:Chernobyl Nuclear Accident; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D007953:Leukemia, Radiation-Induced / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C491901:FAS protein, human; D026901:Membrane Transport Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor