Common gene expression signatures in t(8;21)- and inv(16)-acute myeloid leukaemia

Br J Haematol. 2006 Nov;135(3):336-47. doi: 10.1111/j.1365-2141.2006.06310.x. Epub 2006 Sep 21.

Abstract

Human acute myeloid leukaemia (AML) involving a core-binding factor (CBF) transcription factor is called CBF leukaemia. In these leukaemias, AML1 (RUNX1, PEBP2alphaB, CBFalpha2)-MTG8 (ETO) and CBFbeta (PEBP2beta)-MYH11 chimaeric proteins are generated by t(8;21) and inv(16) respectively. We analysed gene expression profiles of leukaemic cells by microarray, and selected genes whose expression appeared to be modulated in association with t(8;21) and inv(16). In a pair-wise comparison, 15% of t(8;21)-associated transcripts exhibited high or low expression in inv(16)-AML, and 26% of inv(16)-associated transcripts did so equivalently in t(8;21)-AML. These common elements in gene expression profiles between t(8;21)- and inv(16)-AML probably reflect the situation that AML1-MTG8 and CBFbeta-MYH11 chimaeric proteins affect a common set of target genes in CBF leukaemic cells. On the other hand, 38% of t(8;21)-associated and 24% of inv(16)-associated transcripts were regulated in t(8;21)- and inv(16)-specific manners. These distinct features of t(8;21)- and inv(16)-associated genes correlate with the bimodular structures of the chimaeric proteins (CBF-related AML1 and CBFbeta portions, and CBF-unrelated MTG8 and MYH11 portions).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Child
  • Chromosome Inversion / genetics
  • Chromosomes, Human, Pair 16 / genetics
  • Chromosomes, Human, Pair 21 / genetics
  • Cluster Analysis
  • Core Binding Factors / genetics
  • DNA-Binding Proteins / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Leukemic / genetics
  • Genes, Neoplasm / genetics
  • Humans
  • Leukemia, Myeloid / genetics*
  • Neoplasm Proteins / genetics
  • Oncogene Proteins, Fusion / genetics
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins / genetics
  • RUNX1 Translocation Partner 1 Protein
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Transcription Factors / genetics

Substances

  • CBFbeta-MYH11 fusion protein
  • Core Binding Factors
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • RUNX1 Translocation Partner 1 Protein
  • RUNX1T1 protein, human
  • Transcription Factors