Molecular characterization of AML with ins(21;8)(q22;q22q22) reveals similarity to t(8;21) AML

Genes Chromosomes Cancer. 2011 Jan;50(1):51-8. doi: 10.1002/gcc.20830.

Abstract

In acute myeloid leukemia (AML), nonrandom clonal chromosome aberrations are detectable in ∼ 55% of adult cases. Translocation t(8;21)(q22;q22) resulting in the 5'RUNX1/3'RUNX1T1 fusion gene occurs in ∼ 8% of AML cases. Also, ins(8;21) and ins(21;8) have been described that show a broad heterogeneity at the molecular level with inserted fragment sizes ranging from 2.4 to 44 Mb. Microarray-based comparative genomic hybridization (arrayCGH) in 49 intermediate-risk AML and RT-PCR-based screening in 532 AML cases allowed the detection of ins(21;8)/ins(8;21) in three cases; arrayCGH and subsequent RT-PCR revealed an ∼ 0.5 Mb sized inserted fragment generating the 5'RUNX1/3'RUNX1T1 fusion gene in one case with a submicroscopic ins(21;8)(q22;q22q22) whereas the other two cases were identified by banding analysis and RT-PCR, respectively. Gene expression profiling (GEP) and a detailed review of the literature highlighted similar biological features of AML cases with ins(21;8)/ins(8;21) and t(8;21)(q22;q22). Our study demonstrates the potential of high-resolution array-based analysis and GEP and provides further evidence that AML with insertions generating the 5'RUNX1/3'RUNX1T1 fusion not only biologically resemble the t(8;21)(q22;q22) AML subgroup, but might also share its prognostically favorable clinical behavior. Thus, similar treatment options should be considered in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Breakpoints
  • Chromosomes, Human, Pair 21*
  • Chromosomes, Human, Pair 8*
  • Cluster Analysis
  • Comparative Genomic Hybridization
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Genetic Techniques
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins, Fusion / genetics
  • Proto-Oncogene Proteins / genetics
  • RUNX1 Translocation Partner 1 Protein
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Translocation, Genetic*

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • RUNX1 Translocation Partner 1 Protein
  • RUNX1 protein, human
  • RUNX1T1 protein, human
  • Transcription Factors