Cytogenetic Profile and FLT3 Gene Mutations of Childhood Acute Lymphoblastic Leukemia

Abstract

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.

Characteristics of Molecular Genetic Mutations and Their Correlation with Prognosis in Adolescent and Adult Patients with Acute Lymphoblastic Leukemia

“…FLT3 mutations are relatively rare in patients with ALL, with an incidence of 1-7% [19,[27][28][29][30]; they are more common in patients with high diploidy and KMT2A rearrangements [31][32][33]. Univariate analysis in our study revealed that the FLT3 mutation was associated with worse OS, which is consistent with the findings of previous studies that had small samples [19,34,35], However, these studies and ours are limited by the sample size, the short follow-up period, and the different composition of FLT3 mutation types. The effect of the FLT3 mutation on the prognosis of patients with ALL still needs to be confirmed in large-sample clinical studies.…”

Gene Mutations Related to Glucocorticoid Resistance in Pediatric Acute Lymphoblastic Leukemia

“…For instance, Zheng et al reported that FLT3 and TP53 mutations are common in Chinese ALL patients ( 31 ), and Zhang et al reported high rates of FLT3 mutations in B-ALL ( 32 ). In contrast, a lower rate of FLT3 mutations (4–5%) has been reported in international studies ( 33 , 34 ). In our study, all TP53 mutant chromosomes had a normal karyotype, although previous studies have shown that TP53 mutations usually occurred in hypodiploidy.…”

Overview on Aneuploidy in Childhood B-Cell Acute Lymphoblastic Leukemia

“…Similarly, it was 99.7% in the study by Dastugue et al [85]. It is believed that this is related to the potentially greater sensitivity of hyperdiploid lymphocytes to the cytotoxic effects of methotrexate, which is a component of many currently used therapies [28,75,86,87].…”