The distribution of XRCC1Arg 339Gln genotypes showed a significant difference between patients and controls (p=0.025). The presence of at least one XRCC1 399Gln allele indicated an increased risk of AML and the proportion of AML patients homozygous for the Gln/Gln allele was significantly higher than in the control group (p=0.025). However, distributions of the XRCC3 Thr241Met, XPD Lys751Gln, and NQO1Pro 187Ser genotypes were not significantly different between patients and controls. Combined analysis of the studied DNA repair gene polymorphisms did not show an interaction with the detoxification NQO1 Pro187Ser polymorphism.
Janus Kinase 2 (JAK2) is a member of a family of four Janus Kinases, 2, and 3 and tyrosine kinase 2. Mutated JAK2 (V617F) has the ability to activate downstream signal transducer and activator of transcription (STAT)-mediated transcription in the absence of the ligand erythropoietin. The autoinhibitory activity of JAK2 is disrupted by the presence of the V617F mutation. Somatic mutation in JAK2 (V617F) gene has been reported in myeloid disorders. This study reports the prevalence of JAK2V617F using amplification refractory mutation system (ARMS)-polymerase chain reaction in 246 Egyptian patients with different myeloid disorders and studied the relationship between the JAK2V617F mutation and parameters in peripheral blood. The mutation was detected among 88 patients (35.8%) with different myeloid disorders. JAK2V617F was found among 81.4% of polycythemia vera (PV), 50% of essential thrombocythemia, 46.1% of primary myelofibrosis (PMF), 33.3% of philadelphia (Ph)-negative chronic myeloid leukemia, 33.3% of myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN), and 50% of refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) patients. Hemoglobin and white blood cells were significantly higher in the mutated group of MPN including PV, essential thrombocythemia, and PMF, whereas platelet counts were higher among the mutated PV, PMF, RARS-T, and MDS/MPN group. The identification of JAK2V617F mutations has raised the prospect of developing specific JAK2V617F inhibitors to treat mutated patients.
The aim of this study was to detect the possible role of methylene tetrahydrofolate reductase gene polymorphism (MTHFR C677T) in the pathogenesis of lymphoid neoplasms and to investigate the influence of this polymorphism on methotrexate toxicity in adult ALL patients treated with methotrexate maintenance therapy. There was a statistically significant increase in the risk of non-Hodgkin lymphoma in patients with CT genotype (OR, 2.9; 95% CI, 1.3-6.3; P = 0.007) and combined CT + TT genotype (OR, 3.2; 95% CI, 1.5-6.6; P = 0.006). While no significant association was found between this polymorphism and ALL risk. The patients with ALL treated with methotrexate during maintenance therapy were observed for signs of toxicity. MTHFR 677C>T polymorphism (CT + TT) was significantly overrepresented among cases with hepatic toxicity (OR = 15.6; 95% CI, 2.6-81.3; P = 0.001). In addition, they were overrepresented among cases with mucositis, anemia, thrombocytopenia, and leukopenia. However, it did not reach statistical significance level. Further studies on larger number of subjects are necessary. Additional studies on the role of MTHFR gene polymorphism with environment (folate intake) interaction are needed to confirm the role of these genetic polymorphisms.
A significant association was found between the BAFF -871C/T promoter polymorphism and MC, which may indicate that BAFF could be a potential therapeutic target in HCV-MC.
Background: Acute myeloid leukemia (AML) is a genetically heterogeneous disease in which somatic mutations that disturb cellular growth, proliferation, and differentiation accumulate in hematopoietic progenitor cells. TET methylcytosine dioxygenase 2 (TET2) gene mutations have been recognized in AML and appeared to have an adverse prognostic indicator in cytogenetically normal AML patients. Methods: The study was designed to detect the TET2 single nucleotide polymorphism (SNP rs 6843141) in AML patients. Thirty one AML patients were enrolled in this study, median age was 41 years and male to female ratio was 1:1. Twenty five age and sex matched persons were considered a control group. Patients underwent thorough routine workup, Real time PCR for TET2 SNP polymorphism expression with an ABI Prism Genamp 7500 using peripheral blood c-25767872-10, rs 6843141 (UK) was done for all cases and controls. Result: TET2 polymorphism SNP rs 6843141 was detected in all AML cases with 26 (83.9%) patients showing homozygous pattern and 5 (16.1%) patients showing heterozygous pattern while the control group was mostly wild type (11 patients, 44 %) and heterozygous group (11 patients, 44 %), p<0.001. The highest homozygous pattern (19 out of 26 patients, 73%) was present in AML M1, M2 and M5 subtypes, which are the commonest encountered subtypes among our cases. Fifteen out of 27 AML patients were cytogenetically normal (55.5%). TET2 polymorphism showed higher bone marrow blast percentage among homozygous group, p=0.015. Conclusion: TET2 SNP rs 6843141 polymorphism is common among Egyptian AML cases irrespective of their cytogenetic abnormality.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.