Journal of Blood & Lymph

Comprehensive FLT3 analysis in Indian acute myeloid leukaemia

Abstract

Shalvi V. Mehta, Shilin N.Shukla and Hemangini H. Vora

Abstract
Aim: Activating mutations of FLT3 are commonly found in AML patients and reported to be associated with poor
clinical outcome. We aimed to evaluate the incidence of FLT3 mutations along with FLT3 mRNA and CD135 protein
expression in AML patients of western India and their role in prognosis of disease.
Method: Analysis for the detection of FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD)
point mutations and quantification of mRNA level was carried out in total 174 de novo patients diagnosed with acute
myeloid leukemia (AML), myelodysplastic syndrome (MDS) and aplastic anemia using PCR and RT-PCR methods.
FLT3 protein was quantified by flow cytometry on leukemic blasts.
Results: The incidence of FLT3 ITD, FLT3 TKD mutations and CD135 protein expression was found to be 19%,
7% and 62% respectively in AML patients. In MDS, only FLT3 ITD mutation and CD135 protein over expression
could be analyzed, incidence of which was 22% and 60%. In aplastic anemia, FLT3 mutations, FLT3 mRNA and
protein over expression were not detected. FLT3 mutations as well as FLT3 mRNA and protein over expression
were prominently noted in AML subtypes associated with myelo-monocytic lineage. CD135 protein over expression
was significantly associated with reduced Disease Free Survival (DFS) whereas WBC and blasts emerged as poor
prognostic factors with respect to Disease Free Survival (DFS) and Overall Survival (OS) respectively in multivariate
analysis.
Conclusion: Our data suggest that CD135 receptor protein over expression is a potential prognostic marker as
well as molecular target for FLT3 inhibitors in AML patients.