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

Nevine F Shafik; Amira D Darwish; Rasha Mahmoud Allam; Ghada M Elsayed

doi:10.1016/j.clml.2021.05.005

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

Clin Lymphoma Myeloma Leuk. 2021 Oct;21(10):676-685. doi: 10.1016/j.clml.2021.05.005. Epub 2021 May 11.

Authors

Nevine F Shafik¹, Amira D Darwish², Rasha Mahmoud Allam³, Ghada M Elsayed⁴

Affiliations

¹ Clinical Pathology and Oncologic Laboratory Medicine Department, National Cancer Institute, Cairo University, Egypt. Electronic address: nevine.fawzy@nci.cu.edu.eg.
² Medical Oncology Department, National Cancer Institute, Cairo University, Egypt.
³ Cancer Epidemiology and Biostatistics Department, National Cancer Institute, Cairo University, Egypt.
⁴ Clinical Pathology and Oncologic Laboratory Medicine Department, National Cancer Institute, Cairo University, Egypt.

PMID: 34108128
DOI: 10.1016/j.clml.2021.05.005

Abstract

Background: 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.

Patients and methods: 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.

Results: 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.

Conclusion: Initial high total leukocyte count, FLT3-ITD AF, and splenomegaly are independent prognostic factors for poor outcome in FLT3-ITD-positive AML.

Keywords: Acute myeloid leukemia; Allelic ratio; FMS-like tyrosine kinase 3; NPM1; Prognosis.

MeSH terms

Female
Gene Frequency / genetics*
Humans
Leukemia, Myeloid, Acute / genetics*
Male
Prognosis
Treatment Outcome
fms-Like Tyrosine Kinase 3 / metabolism*

Substances

FLT3 protein, human
fms-Like Tyrosine Kinase 3