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

  • Yunus, Noraini Mat (Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia) ;
  • Johan, Muhammad Farid (Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia) ;
  • Al-Jamal, Hamid Ali Nagi (Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia) ;
  • Husin, Azlan (Haemato-Oncology Unit, Department of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia) ;
  • Hussein, Abdul Rahim (Advanced Medical And Dental Institute, Universiti Sains Malaysia) ;
  • Hassan, Rosline (Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia)
  • Published : 2015.07.13

Abstract

Background: Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis. Materials and Methods: We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia. Results: 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 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value = 0.008) and white blood cell count (p-value = 0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value = 0.374). Conclusions: The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.

Keywords

AML;FLT3;ITD;CSGE

Acknowledgement

Supported by : Universiti Sains Malaysia

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