FLT3-ITD and CD135 Over-Expression are Frequent Findings of Poor Survival in Adult Patients with Acute Leukemias

Arch Med Res. 2021 Feb;52(2):217-223. doi: 10.1016/j.arcmed.2020.10.013. Epub 2020 Oct 24.

Abstract

Background: Fms-like tyrosine kinase 3 (FLT3) expression and mutation have been considered a poor prognostic factor in acute myeloid leukemia (AML). FLT3-ITD mutation is present in 30% of adult patients with AML and 2-5% in childhood acute lymphoblastic leukemia (ALL). The impact of these mutations on the prognosis of ALL patients, has not yet been established. Moreover, a limited number of publications regarding the level of expression of the FLT3 receptor (CD135) in both leukemias exist. This study aimed to analyze the clinical outcomes associated to the presence of FLT3-ITD mutation and the expression of CD135.

Methods: 82 adult patients with newly diagnosed acute leukemia (39 with AML and 43 with ALL) were included. Flow cytometry and RT-PCR were done to analyze the expression of CD135 and the presence of FLT3 ITD mutation, respectively.

Results: FLT3-ITD was present in 14 (36%) of AML and 15 (35%) of ALL patients. Disease free survival (DFS) and overall survival (OS) were lower in ALL patients having a CD135 expression >3000 cells/μL. There was a trend for poor OS in AML patients expressing FLT3 ITD. OS was worse in AML patients with high expression of CD135.

Conclusion: A higher (35%) frequency of FLT3-ITD was found in adult ALL patients. The presence of FLT3-ITD was associated with a trend of poor OS in AML cases, and overexpression of CD135 was correlated with poor DFS in ALL cases and poor OS in both acute leukemias.

Keywords: CD135; FLT3 ITD; Lymphoblastic leukemia; Myeloblastic leukemia; Prognostic factors; Survival.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Disease-Free Survival
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Mutation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / biosynthesis
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism*

Substances

  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3