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N. I. Bilous, I. V. Abramenko, A. A. Chumak, I. S. Dyagil, Z. V. Martina
State Institution «National Research Center for Radiation Medicine of the National Academy of Medical
Sciences of Ukraine», 53 Yuriia Illienka St., Kyiv, 04050, Ukraine
STEREOTYPED CASES IN UKRAINIAN COHORT OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS DEPENDING ON THE IONIZING RADIATION EXPOSURE
Objective: to analyze the stereotyped subsets in cohort of Ukrainian chronic lymphocytic leukemia (CLL) patients
in general and depending on the ionizing radiation (IR) exposure.
Methods. Analysis was performed in the groups of 118 CLL patients irradiated due to the Chornobyl NPP accident
(95 clean-up workers, 17 inhabitants of radionuclide contaminated areas, and 6 evacuees) and 294 IR non-exposed
patients. The IGHV (immunoglobulin heavy chain variable region) gene mutational status, mutations of NOTCH1, TP53
and SF3B1 genes were studied by polymerase chain reaction followed by direct sequencing. Associations between
clinical and molecular data of patients were analyzed with the SPSS software package, version 20.0.
Results. The incidence of stereotyped CLL cases in Ukrainian cohort was high (50.5 %) and comparable in IRexposed and non-exposed patients. The ratio of major and minor clusters as well as the frequency of individual clusters was comparable with reported data with some exceptions: a low incidence of subset #2; absence of subset #8;
high frequency of minor subset #V4|J4.5.6|18|5. The distinctive features of IR-exposed CLL patients found were:
1) comparable frequency of stereotyped cases among mutated and unmutated (UM) IGHV genes cases (p = 0.557);
2) lack of differences IGHV gene repertoires among stereotyped and heterogeneous cases (p = 0.508); 3) «heterogeneity» of stereotyped cases: all identified stereotyped clusters, with the exception of cluster #1, consisted of one
case. Stereotyped cases with expression of UM IGHV clan I genes (except IGHV1-69 gene) were more susceptible to the
appearance of NOTCH1 mutations. Patients of cluster #4 were younger, tended to have a longer time-to-treatment
period and overall survival (OS) compared to subset #2. Patients of cluster #2 are more likely to have autoimmune
hemolytic anemia (AIHA) and SF3F1 mutations. IGHV3-21 expression was associated with worse OS in univariate and
multivariate analysis. AIHA was more common in patients with UM IGHV4-59 and IGHV3-11 genes.
Conclusions. The revealed differences in distribution of stereotyped CLL cases in Ukrainian cohort are most likely
to reflect variations in the genetic background, environmental factors (including IR exposure), and their interactions in different geographic areas
Key words: chronic lymphocytic leukemia, IGHV genes, stereotyped subsets, Chornobyl NPP accident.
Problems of Radiation Medicine and Radiobiology.
2022;27:307-323. doi: 10.33145/2304-8336-2022-27-307-323
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