THE EXPRESSION OF THE MAIN AND ALTERNATIVE TRANSCRIPT (SORL1-Δ2) OF THE SORL1 GENE IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS AFFECTED BY THE CHORNOBYL ACCIDENT

Abstract

Objective: to study clinical-hematological data and expression of the main and alternative transcripts of SORL1 gene in chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophe. Methods. Analysis was performed in the main group of 34 CLL patients irradiated due to the Chornobyl NPP accident (30 clean-up workers, and 4 evacuees) and in the control group of 27 non-irradiated CLL patients. Groups of patients were comparable by age, sex, stage of disease, mutational status of IGHV genes. Expression of the main and alternative transcripts of SORL1 gene was evaluated by Quantitative Real-time polymerase chain reaction (PCR). The IGHV gene mutational status, TP53 and SF3B1 mutations were studied by PCR followed by direct sequencing. Data were analyzed with the SPSS software package, version 20.0. Results. Relative expression level of the main transcript of SORL1 gene was low (mean 1.71 ± 0.55, median 0.57), did not correlate with the IGHV gene mutational status, TP53 and SF3B1 mutations, stage of disease. The expression of B transcript was not detected, F transcript was expressed at a very low level in 9 patients. The average relative expression level of SORL1-Δ2 transcript was 14.1 ± 6.04 (median 3.48; range 0.01–90.51). The expression of SORL1-Δ2 transcript above the median was more frequent among patients on C stage (p = 0.001), and in patients with unmutated IGHV genes was associated with an extremely negative course of CLL (median of overall survival 9 months vs 61 months at low expression). Relative expression levels of the main and alternative transcripts of SORL1 gene in patients of the main and the control groups did not differ. Conclusions. Our preliminary data suggest that increased expression of SORL1-Δ2 transcript in CLL patients with unmutated IGHV genes can be considered as a negative prognostic marker. Key words: chronic lymphocytic leukemia, SORL1, SORL1-Δ2, Chornobyl NPP accident.