Research of nitric oxide synthase gene polymorphisms and chromosomal (chromosome no: 10-22 and gender x/y) abberrations by MLPA method in chronic myeloid leukemia

In this study, the aim is to investigate the chromosomal aberrations in Chronic Myeloid Leukemia (CML) in particular, aberrations on chromosome regions of 34 genes related to oncogenes (EMS1, CRK, ERBB2, HRAS etc.), transcription factor (RENT2, NFKBI, RELA etc.), signal transmission (CDKN1B, SPG3A etc.), cytokines (TNFRSF7 etc.), tumor suppressors (BRCA1, MDM2, BRCA2, RB1), and apoptosis regulation (MOAP1, BAX, PDCD8 etc.) using the Multiplex Ligation-dependent Probe Amplification (MLPA) method. Fort his, 48 BCR-ABL positive patients and 15 healthy individuals as control were included. The aberration in 34 genes on different regions of 14 chromosomes were investigated. Moreover 60 BCR-ABL positive patients and 60 individuals as control were used to investigate NOS3 (-894) and NOS3 VNTR gene polymorphisms. Results were analyzed by comparing both among each other and with clinical parameters. Consequently MLPA analyses revealed duplications in Nuclear Factor Kappa B (NFKBI) gene in 5 CML patients and in T-Cell Translocation Gene 2 (LMO2) in 1 CML patient. When age, sokol risk score, splenomegaly, leukocytosis (>50000), and NOS3 gene polymorphism which were all found to affect event-free survival time(p<0.010) in univariate analyses were analyzed in multivariate analyses, all the parameters lost their significance. However, NOS3 (-894) polymorphism was found to be conspicuous among all the other prognostic parameters analyzed (p=0.084) but was not significant. A statistically significant relationship in terms of frequency was observed between GT/TT and GG genotypes in NOS3 (-894) gene according to the sokol risk score and ELN criteria. The control and CML patient groups were compared in the Hardy-Weinberg Equilibrium of NOS3 (-894/VNTR) polymorphism, a deviation from HWE was observed in the patient group but not in the control group. This thesis study is the first study to compare the duplications detected in the 11th and 14th chromosomes in CML and clinical parameters. Nevertheless, NOS3 gene polymorphisms appeared to be significantly related to CML while NFKB dublication was not.