FLT3-ITD Allele Frequency Is an Independent Prognostic Factor for Poor Outcome in FLT3-ITD–Positive AML Patients

Abstract

FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is a molecular genetic alteration significantly affecting the clinical outcome in patients with acute myeloid leukemia (AML). FLT3-ITD mutations are characterized by variable mutant-to-wild allelic ratios (ARs) and sizes of the duplicated sequences. The size of the inserted sequence may vary from a few to hundreds of nucleotides. The aim of this work was to determine the impact of FLT3-ITD ARs, FLT3-ITD allelic frequency (AF), and allele size in de novo AML. We studied 117 patients with FLT3-ITD gene mutation-positive AML, dividing them into those with low ARs and those with high ARs (>0.64) and examined their prognostic impact. High FLT3-ITD AR ≥ 0.64 and AF ≥ 0.5 were significantly associated with a lower overall survival compared with lower AR (median 0.625 vs. 1.020 months, respectively; P=.041) and AF (median 0.493 vs. 0.954 months, respectively; P=.009). NPM1 mutation had no favorable impact on the low-level FLT3-ITD group. Initial high total leukocyte count, FLT3-ITD AF, and splenomegaly are independent prognostic factors for poor outcome in FLT3-ITD-positive AML.