رسائل ماجيستير
English
2017
Frequency of C-Kit D816V and FLT3-ITD Mutations in Sudanese patients with Acute Myeloid Leukemia
Elshazali Widaa Ali, ندى داوود الزبير أحمد
كلية الدراسات العليا-جامعة النيلين · السودان
Acute myeloid leukemia (AML) is a clonal hematopoietic disorder that is frequently associated with genetic instability characterized by a diversity of chromosomal and molecular changes.Receptor tyrosine kinases (RTKs) are involved in different steps of neoplastic development and progression. Their signal¬ing influences the growth, differentiation, adhesion, motility, and death of cells. RTKs are divided into 20 subfamilies including class III RTKs. Mutations in class III RTKs have a major impact on leukemic transformation of acute myeloid leukemia (AML) cells. Class III RTKs include among others c-Kit, colony-stimulating factor 1 receptor (CSF1R), fms-related tyrosine kinase 3 (FLT3), and platelet-derived growth factor receptor α/β (PDGFR α/β). Mutations of fms-like tyrosine kinase 3 (FLT3) and KIT genes, however, result in autonomously leukemic cell proliferation and an unfavorable prognosis.Objective: To determine the frequency of C-kit D816V and FLT3 ITD mutations among Sudanese patients with AML and to correlate these mutations with patients' hematological and demographic data and AML subtypes.Materials and Methods: The study included 72 Sudanese patients with AML. Two and half milliliter (ml) of venous blood was collected from each patient in EDTA container for hematological and molecular analysis. Genomic DNA was extracted by salting out protocol, and then all samples were analyzed for FLT3-ITD mutation using conventional polymerase chain reaction (PCR) and C-kit mutation using Allele specific– competitive blocker PCR assay. Data was analyzed by statistical package for social sciences (SPSS), version 20.Results: A total of 72 Sudanese patients diagnosed with AML were enrolled in this study; 19(43.2%) were males and 25 (56.8%) were females. Sixty (83%) of the patients were adults and 12(17%) were children. Total WBCs count was ranged between 2.1-280×103/µl (Mean±SD: 40.3±58.6).and blast percentage was between 23-90% (Mean±SD:54±19.7).The results showed that, while FLT3-ITD mutation was totally absent (0%), C-kitD816V mutation was found in 33% of the patients.No statistically significant difference was found in mean age (P.value≤ 0.50), blast percentage (P.value= 0.44), and total WBCS count (P.value= 0.050) when compared in patients with and without c-kit mutation.The results showed no statistically significant association between C-kitD816V mutation and each of gender (P.value = 0.31) and subclass of AML (P.value= 0.79).Conclusion: C-Kit D816V mutation was found in 33% of Sudanese patients with AML whereas FLT3 –ITD mutation was totally absent. C-kit mutation has no effect on age of incidence, T.WBCs count, and blast percentage. No association was found between c-kit mutation and patients' gender, or subclass of AML.
