-
[show abstract]
[hide abstract]
ABSTRACT: Acute myeloid leukemia (AML) can develop as a secondary malignancy following radiotherapy, but also following low-dose environmental or occupational radiation exposure. Therapy-related AML frequently carries deletions of chromosome 5q and/or 7, but for low-dose exposure associated AML this has not been described. For the present study we performed genome-wide screens for loss-of-heterozygosity (LOH) in a set of 19 AML cases that developed after radiation-exposure following the Chernobyl accident. Using Affymetrix SNP arrays we found large regions of LOH in 16 of the cases. Eight cases (42%) demonstrated LOH at 5q and/or 7, which is a known marker of complex karyotypic changes and poor prognosis. In accordance with literature data, the overall survival for these patients was significantly shorter as compared to patients without this alteration (P=0,014). We could show here for the first time that exposure to low-dose ionizing radiation induces AML with molecular alterations similar to those seen in therapy-related cases.
Genes. 05/2011; 2(2):384-393.
-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: To present previously unavailable data on the use of stem cell administration to aid recovery of victims of the Chernobyl disaster. On 26 April 1986, an accident at Unit 4 of the Chernobyl Nuclear Power Plant took place during the planned test of one of the safety systems. The diagnosis of acute radiation syndrome (ARS) was confirmed in 134 individuals exposed to high levels of radiation. There were nine patients heretofore unreported in the scientific literature who underwent intraosseous injections of allogeneic bone marrow cells in Kyiv. CONCLUSIONS: Transplantation was associated with significantly shortened time to recovery of granulocyte and platelet counts in these patients. While current guidelines would certainly include the use of cytokines, these data provide an indication of the effectiveness of stem cell transplant to treat victims of radiation exposure.
International Journal of Radiation Biology 03/2011; 87(8):846-50. · 2.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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).
General Physiology and Biophysics 04/2009; 28(1):63-9. · 1.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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 overex-pressed antiapoptotic protein Bcl-2 (12/21 vs. 6/35, р < 0.005) and less often demonstrated expression of Fas receptor (12/21 vs. 30/35, р < 0.05). Moreover, leukemic cells were simultaneously Fas nega-tive and Bcl-2 positive in 4 out of 21 patients exposed to ionizing radiation but none of spontane-ous cases had similar phenotype (р < 0.05). Patients with radiation-associated AML compared to spontaneous cases more often were P-glycoprotein positive (12/20 vs. 9/31, р < 0.05). P-glycoprotein overexpression significantly correlated with the resistance of the disease to chemotherapy in patients with radiation-associated AML (р < 0.05).
-
Sergiy V Klymenko,
Karin Bink,
Klaus R Trott,
Vladimir G Bebeshko,
Dimitry A Bazyka,
Iryna V Dmytrenko,
Iryna V Abramenko,
Nadia I Bilous,
Horst Zitzelsberger,
Andrei V Misurin,
Michael J Atkinson,
Michael Rosemann
[show abstract]
[hide abstract]
ABSTRACT: Although acute myelogenous leukemia (AML) arising after radiation exposure is considered to be secondary, little is known about the molecular mechanisms by which the radiation induces the leukemogenic phenotype. The aim of the study was to analyze whether the MLL translocations are as frequent in radiation-associated AML as in spontaneous AML cases.
Sixty one AML samples obtained at diagnosis were analyzed for the presence of MLL abnormalities using fluorescent in situ hybridization and/or reverse transcription polymerase chain reaction. Of these patients, 27 had experienced radiation exposure due to the Chernobyl accident, 32 were non-irradiated (spontaneous AML), and 2 developed therapy-related AML after chemotherapy with topoisomerase II inhibitors.
MLL gene translocations were detected in both groups of spontaneous and therapy-related AML (1/32 and 1/2 cases respectively). The sole MLL rearrangement found in the group of radiation-associated AML patients was a duplication of the gene.
Our data preclude the involvement of MLL gene translocations in radiation-induced leukemogenesis, but support the assumption that loss and gain of chromosomal material could be crucial in the leukemogenesis of AML patients with the history of radiation exposure due to the Chernobyl accident.
Experimental oncology 04/2005; 27(1):71-5.
