FLT3-TKD Mutations Associated With NPM1 Mutations Define a Favorable-risk Group in Patients With Acute Myeloid Leukemia

Clin Lymphoma Myeloma Leuk. 2018 Dec;18(12):e545-e550. doi: 10.1016/j.clml.2018.06.006. Epub 2018 Jun 13.

Abstract

Background: Outcome of patients with mutation of the FLT3 tyrosine kinase domain (FLT3-TKD) in acute myeloid leukemia (AML) remains controversial.

Patients and methods: Herein, we present a retrospective study of 126 newly diagnosed patients with AML performed in 2 French centers.

Results: FLT3-TKD mutations represented 12.7% of patients, whereas FLT3-internal tandem duplication (ITD) mutation was observed in 20.6% of AML cases and 1.6% of patients harbored both anomalies. At diagnosis, FLT3-TKD and FLT3-ITD were associated with higher peripheral leukocytes count and a higher blast count in bone marrow (P < 10-4). Mutations of the NPM1 gene were frequently associated to FLT3-TKD (68.7%) and FLT3-ITD (61.5%) mutations compared with FLT3 wild type (WT) patients (P < 10-4). Patients with both FLT3-TKD and NPM1 mutations (n = 12; 9.5%) showed a favorable outcome. Interestingly, mutations in NPM1 gene lost their favorable prognostic when not associated with FLT3-TKD both in univariate and multivariate analyses.

Conclusion: Our data suggest that FLT3-TKD mutations should be routinely determined at the time of diagnosis. In association with NPM1 mutations, patients should follow the therapeutic schedule of favorable-risk patients with AML.

Keywords: Chemotherapy; FLT3-ITD mutation; Favorable risk-group; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Combined Modality Therapy
  • Cytogenetic Analysis
  • Female
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Mutation*
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Prognosis
  • Protein Interaction Domains and Motifs / genetics*
  • Retrospective Studies
  • Tandem Repeat Sequences*
  • Treatment Outcome
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors
  • fms-Like Tyrosine Kinase 3 / chemistry
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • Biomarkers, Tumor
  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3