The Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that plays a key role in cell survival, proliferation, and differentiation of hematopoietic stem cells. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia (AML). AML patients with FLT3 internal tandem duplication (ITD) mutations have poor cure rates the prognostic significance of point mutations; tyrosine kinase domain (TKD) is still unclear. We analyzed the frequency of FLT3 mutations (ITD and D835) in patients with AML at diagnosis; no sufficient data currently exist regarding FLT3 mutations in Saudi AML patients. This study was aimed at evaluating the frequency of FLT3 mutations in patients with AML and its significance for prognosis. The frequency of FLT3 mutations in our study (18.56%) was lower than many of the reported studies, FLT3-ITD mutations were observed in 14.4%, and FLT3-TKD in 4.1%, of 97 newly diagnosed AML patients (82 adult and 15 pediatric). Our data show significant increase of FLT3 mutations in male more than female (13 male, 5 female). Our results support the view that FLT3-ITD mutation has strong prognostic factor in AML patients and is associated with high rate of relapse, and high leucocytes and blast count at diagnosis and relapse.
The fms-like tyrosine kinase 3 (FLT3) gene is a member of the class III receptor tyrosine kinase family. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia.Currently, there is no published data on FLT3 mutations in Saudi acute lymphoblastic leukemia (ALL) patients.In this retrospective study, we have examined a cohort of 77 ALL patients to determine the prevalence of FLT3 mutations and the possible prognostic relevance of these mutations in ALL patients. Correlations to other biologic factors such as karyotype, molecular mutations, and leukocyte count were also considered.FLT3 internal tandem duplication (ITD) mutations and point mutation in tyrosine kinase domain (D835) were analyzed in ALL patients, at diagnosis, by polymerase chain reaction (PCR).Two cases (2.6%, 2/77) were positive for FLT3 mutations; one was found to have FLT3/ITD and the other FLT3/D835.Our findings suggest that FLT3 mutations are not common in Saudi ALL and do not affect clinical outcome.
Background:Childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers.Aims:There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results.Materials and methods:Patients—We reviewed all cases from 2007 to 2016 with an established diagnosis of childhood ALL. Of the 110 patients, 98 were B-lineage ALL and 12 T-cell ALL. All the patients were treated by UKALL 2003 protocol and risk stratified according previously published criteria. Cytogenetic analysis—Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Analysis of FLT3 mutations—Bone marrow or blood samples were screened for FLT3 mutations (internal tandem duplications, and point mutations, D835) using polymerase chain reaction methods.Result:Cytogenetic analysis showed chromosomal anomalies in 68 out of 102 cases with an overall incidence 66.7%. The most frequent chromosomal anomalies in ALL were hyperdiploidy, t(9;22), t(12;21), and MLL gene rearrangements. Our data are in accordance with those published previously and showed that FLT3 mutations are not common in patients with ALL (4.7%) and have no prognostic relevance in pediatric patients with ALL. On the contrary, t(9;22), MLL gene rearrangements and hypodiploidy were signs of a bad prognosis in childhood ALL with high rate of relapse and shorter overall survival compared with the standard-risk group (P = .031).The event-free survival was also found to be worse (P = .040).Conclusions:Our data are in accordance with those published previously, confirming the overall frequency of cytogenetic abnormalities and their prognostic relevance.
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