Morphological, cytogenetic and molecular characterisation of FLT3 mutations in Pakistani patients with de novo acute myeloid leukaemia: A single centre experience.

Abstract

Introduction: Mutations in FLT3 are the most commonly reported genetic changes in AML patients. These mutations are normally identified in approximately one third of newly diagnosed patients and are reported to have prognostic significance.

Materials and methods: Peripheral blood samples was collected from 63 AML patients to study their morphological, cytogenetic and molecular features. PCR was used to determine the prevalence of FLT3 mutations; internal tandem duplication (ITD) and tyrosine kinase domain (TKD) in AML patients.

Results: Among 63 AML patients, 42 were males and 21 were females with male to female ratio 2:1 with median age of 32 years. AML-M2 was the predominant French-American-British (FAB) subtype (42%) followed by M4 (27%), M3 (8%), M1 (8%), M0 (8%) and M5 (7%) respectively. Cytogenetic analysis of 60 patients showed 58% as cytogenetically normal (CN) whereas 42% had aberrant karyotype.The most frequent aberrations were trisomy8, t(8;21), t(15;17) (8.3%) each, inversion16 (5%), and different deletions (12%) respectively. FAB-M4 subtype showed most of the chromosomal anomalies. Among 63 AML patients, 22% showed FLT3/ITD while 6.4% had D835 mutation after molecular analysis. FLT3 mutations were found in most of the FAB subtypes and cytogenetic groups. FLT3/ITD mutations were more common in patients with normal karyotype (26%) and usually present with hyperleukocytosis but association between two was not significant.

Conclusion: The cytogenetic data of adult AML from Pakistan showed presence of favourable prognostic karyotype with comparable prevalence as reported in international data. Moreover, FLT3/ITD mutations are commonly found in our patients as determined by molecular analysis. Therefore, inclusion of this unfavourable prognostic marker should be routine in molecular diagnostic testing of AML.