EVI1-rearranged acute myeloid leukemias are characterized by distinct molecular alterations

Blood. 2015 Jan 1;125(1):140-3. doi: 10.1182/blood-2014-07-591529. Epub 2014 Oct 20.


The genetic and transcriptional signature of EVI1 (ecotropic viral integration site 1)-rearranged (EVI1-r) acute myeloid leukemias (AMLs) remains poorly defined. We performed RNA sequencing of 12 EVI1-r AMLs and compared the results with those of other AML subtypes (n = 139) and normal CD34(+) cells (n = 17). Results confirm high frequencies of RAS and other activated signaling mutations (10/12 AMLs) and identify new recurrent mutations in splicing factors (5/12 AMLs in SF3B1 and 2/12 AMLs in U2AF1), IKZF1 (3/12 AMLs), and TP53 (3/12 AMLs). Mutations in IKZF1, a gene located on chromosome 7, and monosomy 7 are mutually exclusive in this disease. Moreover IKZF1 expression is halved in monosomy 7 leukemias. EVI-r AMLs are also characterized by a unique transcriptional signature with high expression levels of MECOM, PREX2, VIP, MYCT1, and PAWR. Our results suggest that EVI1-r AMLs could be molecularly defined by specific transcriptomic anomalies and a hitherto unseen mutational pattern. Larger patient cohorts will better determine the frequency of these events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic*
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Ikaros Transcription Factor / genetics
  • Leukemia, Myeloid, Acute / genetics*
  • MDS1 and EVI1 Complex Locus Protein
  • Mutation*
  • Nuclear Proteins / genetics
  • Proto-Oncogenes / genetics*
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcriptome
  • Tumor Suppressor Protein p53 / genetics
  • Vasoactive Intestinal Peptide / genetics


  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • Guanine Nucleotide Exchange Factors
  • IKZF1 protein, human
  • MDS1 and EVI1 Complex Locus Protein
  • MECOM protein, human
  • MYCT1 protein, human
  • Nuclear Proteins
  • PREX2 protein, human
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • prostate apoptosis response-4 protein
  • Ikaros Transcription Factor
  • Vasoactive Intestinal Peptide