Objective: to determine the association between the expression of lipoprotein lipase (LPL) and c-MYC genes inperipheral blood cells of chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophedepending on the mutational status of IGHV genes.
Methods: Analysis was performed in the group of 69 CLL patients irradiated due to the Chornobyl NPP accident (58clean-up workers of 1986 year, 6 inhabitants of radionuclide contaminated areas, and 5 evacuees). The IGHV genemutational status was studied by polymerase chain reaction (PCR) followed by direct sequencing. LPL and c-MYCexpression was evaluated by Quantitative Real-time PCR. Data were analyzed with the SPSS software package, version 20.0.
Results: Relative LPL expression levels in CLL samples ranged from 0 to 1663.5 (mean 138.47 ± 30.69, median 26.1).A strong correlation between individual LPL expression levels and IGHV mutational status was found (r = 0.684;p < 0.0001). The average relative c-MYC expression level was 5.7 ± 0.87 (median 2.86; range 0-48.5). No association between c-MYC expression and IGHV mutational status was found. Among unmutated IGHV cases, a correlationbetween LPL and c-MYC gene expression levels was identified: r = 0.351; p = 0.013.
Conclusions: Our data confirm the dominant concept that unmutated IGHV CLL cases are more sensitive to the actionof proliferative stimuli compared to mutated IGHV CLL cases. This is manifested by an increase in the expression ofa functionally significant LPL gene, is one for the strongest negative prognostic markers in CLL.
Meta: vyznachyty asotsiatsiiu mizh ekspresiieiu geniv lipoproteïnlipazy (LPL) i c-MYC u peryferychniĭ krovi khvorykhna khronichnu limfotsytarnu leĭkemiiu (KhLL), iaki postrazhdaly vnaslidok Chornobyl's'koï katastrofy, zalezhno vidmutatsiĭnogo statusu IGHV geniv.Metody. Doslidzhennia provedeno u grupi 69 khvorykh na KhLL, oprominenykh vnaslidok avariï na Chornobyl's'kiĭAES (58 uchasnykiv likvidatsiï naslidkiv avariï 1986 r., 6 meshkantsiv terytoriĭ, kontaminovanykh radionuklidamy,5 evakuĭovanykh). Mutatsiĭnyĭ status IGHV geniv doslidzhuvaly za dopomogoiu polimeraznoï lantsiugovoï reaktsiï(PLR) z nastupnym sekvenuvanniam. Ekspresiiu geniv LPL i c-MYC otsiniuvaly metodom PLR u real'nomu chasi. Otrymani dani analizuvaly u statystychniĭ programi SPSS software package, version 20.0.Rezul'taty. Vidnosnyĭ riven' ekspresiï gena LPL kolyvavsia v mezhakh vid 0 do 1663,5 (138,47 ± 30,69, mediana 26,1).Vyiavlena dostovirna koreliatsiia mizh okremymy rivniamy ekspresiï LPL i mutatsiĭnym statusom IGHV geniv (r = 0,684;p < 0,0001). Vidnosnyĭ riven' ekspresiï c-MYC stanovyv 5,7 ± 0,87 (mediana 2,86; kolyvannia vid 0 do 48,5). Asotsiatsiï mizh rivnem c-MYC ekspresiï ta mutatsiĭnym statusom IGHV geniv ne vyiavleno. Sered khvorykh na KhLL z nemutovanymy IGHV genamy sposterigalas' koreliatsiĭna zalezhnist' mizh ekspresiieiu geniv LPL i c-MYC (r = 0,351; p = 0,013).Vysnovky. Otrymani dani pidtverdzhuiut' dominuiuchu kontseptsiiu vidnosno bil'shoï chutlyvosti vypadkiv KhLL z nemutovanymy IGHV genamy, porivniano z mutovanymy, do diï proliferatyvnykh stymuliv, shcho suprovodzhuiet'sia pidvyshchenniam ekspresiï funktsional'no znachushchogo LPL, odnogo z naĭbil'sh chitkykh markeriv negatyvnogo prognozu perebigu KhLL.
Keywords: Chornobyl NPP accident; IGHV genes; LPL; c-MYC; chronic lymphocytic leukemia.
N. I. Bilous, I. V. Abramenko, A. A. Chumak, I. S. Diagil, Z. V. Martina.