title: Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia.
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.
  
  
  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.
authors.affiliation: Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia E-mail : faridjohan@usm.my.
authors.forename: Noraini Mat
authors.initials: NM
authors.lastname: Yunus
authors.forename: Muhammad Farid
authors.initials: MF
authors.lastname: Johan
authors.forename: Hamid
authors.initials: H
authors.lastname: Ali Nagi Al-Jamal
authors.forename: Azlan
authors.initials: A
authors.lastname: Husin
authors.forename: Abdul Rahim
authors.initials: AR
authors.lastname: Hussein
authors.forename: Rosline
authors.initials: R
authors.lastname: Hassan
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D017386:Sequence Homology, Amino Acid; D015996:Survival Rate; D020080:Tandem Repeat Sequences / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3