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FLT3-ITD Allele Frequency Is an Independent Prognostic Factor for Poor Outcome in FLT3-ITD-Positive AML Patients
Nevine F Shafik1, Amira D Darwish2, Rasha Mahmoud Allam3
1Clinical Pathology and Oncologic Laboratory Medicine Department, National Cancer Institute, Cairo University, Egypt.
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.
Insights
High allelic ratios (ARs) and allelic frequencies (AFs) of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) correlate with poorer survival. These FLT3-ITD characteristics, along with high leukocyte counts and splenomegaly, are key prognostic factors.
Area of Science:
- Hematology
- Molecular Genetics
- Oncology
Background:
- FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is a key genetic alteration in acute myeloid leukemia (AML).
- FLT3-ITD mutations exhibit diverse allelic ratios (ARs) and duplicated sequence sizes.
- Understanding the prognostic impact of FLT3-ITD ARs and allelic frequency (AF) is crucial for AML patient outcomes.
Purpose of the Study:
- To investigate the prognostic significance of FLT3-ITD allelic ratios (ARs), allelic frequencies (AFs), and allele sizes in de novo acute myeloid leukemia (AML).
Main Methods:
- Analysis of 117 de novo AML patients with FLT3-ITD mutations.
- Stratification of patients based on high (>0.64) versus low FLT3-ITD ARs.
- Evaluation of the association between FLT3-ITD characteristics and overall survival.
Main Results:
- High FLT3-ITD AR (≥0.64) and AF (≥0.5) were significantly linked to reduced overall survival.
- Patients with high FLT3-ITD AR had a median survival of 0.625 months compared to 1.020 months for those with low AR (P=.041).
- NPM1 mutations did not confer a favorable prognosis in patients with low-level FLT3-ITD mutations.
Conclusions:
- Elevated FLT3-ITD allelic frequency and ratio are independent prognostic indicators of poor outcome in AML.
- Initial high total leukocyte count, FLT3-ITD AF, and splenomegaly are critical prognostic factors for FLT3-ITD-positive AML patients.
