MOLECULAR GENETIC ABNORMALITIES IN THE GENOME OF PATIENTS WITH Ph-NEGATIVE MYELOPROLIFERATIVE NEOPLASIA AFFECTED BY IONIZING RADIATION AS A RESULT OF THE CHORNOBYL NUCLEAR ACCIDENT

Abstract

Objective. to determine the frequency of major somatic mutations in the JAK2, MPL and CALR genes in the genome of patients with Ph-negative myeloproliferative neoplasms that occur in individuals who have been exposed to ionizing radiation as a result of the Chornobyl accident. Materials and methods. Molecular genetic analysis of genomic DNA samples isolated from blood was performed in 90 patients with Ph-negative myeloproliferative neoplasia (MPN) with a history of radiation exposure and 191 patients with spontaneous MPN utilizing allele-specific polymerase chain reaction (PCR). Results. The presence of major mutations in the genes JAK2, CALR and MPL was revealed in patients with MPN with a history of radiation exposure with a frequency 58.9 % (53 of 90), 12.2 % (11 of 90), and 0 % respectively, and without exposure with frequency 75.4 % (144 of 191), 3.1 % (6 out of 191) and 1.6 % (3 out of 191) respectively. Mutations JAK2 V617F in patients with spontaneous MPN were observed in each clinical form: polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). CALR mutations were detected exclusively in patients with PMF and ET, significantly more often in groups with a radiation exposure history (18.9 % and 33.3 %, vs. 4.2 % and 6.5 %) than without one. At the same time, the occurence of MPL mutations was determined only in patients with spontaneous MPN in 1.6 % of casees. Triple negative mutation status of genes JAK2, MPL and CALR prevailed in the group of patients with MPN with a history of radiation exposure and was 27.8 %, against 16.2 % in patients without radiation exposure (p = 0.05). Conclusions. Genomic research of patients with Ph-negative MPN revealed features of molecular genetic damage in those patients who were exposed to IR as a result of the Chornobyl accident and those with spontaneous MPN. The data obtained by determining of JAK2, MPL and CALR genes mutational status in the genome of patients with MPN is necessary to expand the understanding of the mechanism of leukogenesis, especially caused by radiation. Key words: myeloproliferative neoplasia, polycythemia vera, essential thrombocythemia, primary myelofibrosis, JAK2 V617F, MPL and CALR, ionizing radiation.