Correlation between FLT3-ITD status and clinical, cellular and molecular profiles in promyelocytic acute leukemias

Leuk Res. 2015 Feb;39(2):131-7. doi: 10.1016/j.leukres.2014.11.010. Epub 2014 Nov 27.

Abstract

Internal tandem duplications (ITD) of FLT3 gene occur in about a third of acute promyelocytic leukemias (APL). We investigated the patterns of blood count, surface antigen, expression, chromosome aberrations, PML-RARa isoform, gene expression profile (GEP) and survival in 34 APL patients according to FLT3-ITD status. 97% had a t(15;17) and all of them carried PML-RARa gene fusion, 8 (23.5%) had a FLT3-ITD mutation. Presence of ITD was associated with higher Hb and WBC levels, bcr3 isoform, CD34 expression, CD2 or CD2/CD34 expression. In a multivariate analysis, Hb>9.6g/dL and WBC≥20 × 10(9)/L were important factors for predicting ITD presence. GEP showed that FLT3-ITD carriers clustered separately, even when as few as 5 genes were considered. This study provides further evidence that FLT3-ITDs carriers constitute a biologically distinct group of APL patients.

Keywords: 17); AML M3; Acute promyelocytic leukemia; FLT3–ITD; PML–RARA; t(15.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / biosynthesis
  • Antigens, CD34 / genetics
  • CD2 Antigens / biosynthesis
  • CD2 Antigens / genetics
  • Chromosomes, Human, Pair 15 / genetics
  • Chromosomes, Human, Pair 17 / genetics*
  • Gene Expression Regulation, Leukemic / genetics
  • Humans
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology*
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Translocation, Genetic
  • fms-Like Tyrosine Kinase 3 / genetics*
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Antigens, CD34
  • CD2 Antigens
  • Oncogene Proteins, Fusion
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3