FLT3 VARIANTS IN PATIENTS WITH ACUTE MYELOID LEUKEMIA FROM AMAZONAS STATE, BRAZIL

Abstract

Background: Acute Myeloid Leukemia a cancer of the blood and bone marrow (BM), characterized by accumulation of leukemic blasts in the BM and peripheral blood. Among the variants identified in the AML, mostly occurs in the gene FMS-like tyrosine kinase 3 (FLT3), occurring approximately 10-30% of the cases. FLT3 variants, as in-frame duplications of 3 to >400 base pairs, known as internal tandem duplications (ITDs) and tyrosine kinase domain (TKD) are more prevalent, 25% and 7-10%, respectively. Objective: We investigated genetic variants in the FLT3 in patients with AML, also evaluated possible association of the FLT3 variants with clinical and laboratory data. Methods: The study population was composed of 18 AML patients. The nucleotide sequencing was performed in bone marrow samples, sequencing directed for ITD and TKD region (exon 9-24). Results: The patients included, ten (56%) are females and eight (44%) males, being twelve (67%) primary AML patients, three (16.5%) secondary AML and three patients (16.5%) with relapsed. The missense variants in the FLT3 were identified in four patients: Y416N (exon 10), V557I (exon 13), A680V (exon 16), Y702S (exon 17) and FLT3-ITD (exon 14). The FLT3+ variants were observed in two patients (50%) with secondary AML, one patient (25%) with secondary AML to myelodysplasia and one patient (25%) with relapsed. According to hematological data, the percentage of blasts was higher in FLT3+ patients when compared to FLT3− patients, 40.25% (±31.35) and 35.23% (±30.5), respectively. The white blood cell count was high in FLT3− patients when compared to FLT3+ patients [14,500 mm3 (2,300-61,390) vs 10,225 mm3 (5,210-10,808)], however low red blood cell count was observed in FLT3+ patients 2.6 mm3 (±0.77), 2.96 mm3 (±0.39) in FLT3− patients. Moreover, hemoglobin was higher in FLT3+ patients when compared to FLT3− patients [9,6 g/dL (5,9 -10,8) vs 8,3 g/dL (7,0- 10,6)], as well, platelet count in FLT3+ patients [48,500 mm3 (25,500-65,500) vs 35,000 mm3 (15,000-51,000)]. Discussion: Previous studies have reported that the frequency FLT3 variants occurs in approximately 10-30% of the AML cases, in this study was observed in 22% of the cases. Different studies highlight the FLT3-ITD as variant more prevalent of the FLT3, however, here related the TKD and extracellular domain variants as more prevalent with 50% and 30%, respectively. These found may be due to the features of the study population in our region from Amazonas. Conclusion: Variants different are identified in the FLT3, we highlight the importance to investigate other variants located in the FLT3 exome in AML patients, as well as, to evaluate possible association with change hematological, as platelet and red blood cell count.