Evaluating the clinical significance of FLT3 mutation status in Syrian newly diagnosed acute myeloid leukemia patients with normal karyotype

Abstract

The FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) is one of the most prevalent mutations, affecting between 20 and 30 percent of cases in patients with acute myeloid leukemia (AML). The Patients with a FLT3-ITD mutation have a poor prognosis. In the present study, we investigated the FLT3 (ITD-TKD) mutations in 100 newly adult Syrian patients with AML-Normal karyotype (NK). Our results revealed that prevalence of FLT3-ITD mutation was 24%. Interestingly, 20 patients had a typical duplication mutation and four patients had different mutations. From those four mentioned patients, two of them carried a 39 base pair (bp) duplication in different location: (c.1838_1877dup39, p.591–603dup) and (c.1836_1874 dup 39, p.591–603dup), the third patient, showed FLT3-ITD duplication and a newly insertion together, this insertion was not demonstrated before: (c.1842_1865dup24, c.1865_1866insGAA). Finally, the fourth patient exhibited a duplication of 21bp (c.1855_1875dup21, p.597–603dup). In addition, statistically significant differences were observed for the relation between the presence of FLT3-ITD mutation and lactate dehydrogenase (LDH) level, overall survival (OS), relapse, and event free survival (EFS). We demonstrated that our patients with FLT3-ITD mutation had a poor prognosis. Also, the frequency of FLT3-TKD mutation was low 2% and no compound between the two mutations was found, as individuals showed to carry the two mutations were not detected. These findings are likely useful for a better understanding of molecular leukemogenetic steps in AML-NK patients and may be beneficial for clinical relevance for risk grouping, study design and choice of therapy in Syrian population.