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Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
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[Clinical Characteristics and Prognosis of Acute Myeloid Leukemia with FLT3-ITD Mutation]

Yan Liu1, Xiao-Yan Ke1, Jing Wang1

  • 1Department of Hematology, Peking University Third Hosital, Beijing 100191,China.

Zhongguo Shi Yan Xue Ye Xue Za Zhi
|April 19, 2018
PubMed
Abstract

Insights

The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation is common in acute myeloid leukemia (AML) and associated with poorer outcomes. Patients with this mutation show higher white blood cell counts and lower response rates to initial chemotherapy.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy.
  • The FMS-like tyrosine kinase 3 (FLT3) gene plays a crucial role in hematopoietic stem cell proliferation and differentiation.
  • Internal tandem duplications (ITDs) in the FLT3 gene are common activating mutations in AML.

Purpose of the Study:

  • To investigate the clinical characteristics of AML patients with FLT3-ITD mutations.
  • To evaluate the treatment response and survival outcomes in FLT3-ITD mutated AML patients.

Main Methods:

  • Retrospective analysis of 128 newly diagnosed AML patients (excluding M3 type).
  • FLT3-ITD mutation status determined by polymerase chain reaction (PCR) and gene sequencing.
  • Comparison of clinical features, treatment response (CR+PR), and overall survival (OS) between FLT3-ITD mutated and non-mutated groups.

Main Results:

  • FLT3-ITD mutation was identified in 19.59% (19/97) of evaluable patients.
  • FLT3-ITD group exhibited significantly higher median white blood cell count, peripheral blast percentage, and LDH levels.
  • Lower complete remission (CR) + partial remission (PR) rates (31.6% vs 64.9%) and significantly shorter OS (5 vs 18 months) were observed in the FLT3-ITD group.
  • Higher frequency of concomitant NPM1 mutation in FLT3-ITD positive patients.

Conclusions:

  • FLT3-ITD is a prevalent mutation in AML, often co-occurring with NPM1 mutations.
  • FLT3-ITD positive AML is characterized by aggressive clinical features and poor response to standard induction chemotherapy.
  • Patients with FLT3-ITD mutations have significantly worse overall survival.

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