Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia

Abstract

<b>Background:</b> Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferationvia activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most commongene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated withpoor prognosis. Materials and <br/><b>Methods</b>: We performed mutational analysis of exons 14-15 and 20 of the FLT3gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencinganalysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan,Northeast Peninsular Malaysia. <br/><b>Results</b>: FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%)whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 ofthe juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blastpercentage (p-value = 0.008) and white blood cell count (p-value = 0.023) but there was no significant differencein median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value = 0.374). <br/><b>Conclusions</b>: Theincidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Westernworld and has a significant association with WBC and blast percentage.