Molecular variability of FLT3/ITD mutants and their impact on the differentiation program of 32D cells: implications for the biological properties of AML blasts

Leuk Res. 2009 Oct;33(10):1409-16. doi: 10.1016/j.leukres.2009.01.004. Epub 2009 Jan 31.

Abstract

FLT3 is the most frequently mutated gene in acute myeloid leukemia (AML), with internal tandem duplications (ITDs) accounting for up to 30% of its mutations. To analyze the impact of individual ITDs on the expression profile of immature myeloid cells, we have established 32D cell lines expressing nine different FLT3/ITDs isolated from AML patients and subjected them to whole genome expression profiling and 2DE/LC/MS proteomics. Our data indicate that in comparison to the controls, FLT3/ITD-positive 32D cells exhibit less mature expression profiles resembling early hematopoietic progenitors. Moreover, our results suggest that there exist biological differences among individual ITD variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blast Crisis / genetics*
  • Blast Crisis / pathology*
  • Blotting, Western
  • Cell Differentiation
  • Cell Division
  • Cell Line, Tumor
  • Cloning, Molecular
  • Exons
  • Gene Expression Profiling
  • Genetic Variation*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Mice / genetics
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tandem Repeat Sequences / genetics*
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

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