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

Vincent-Philippe Lavallée, Patrick Gendron, Sébastien Lemieux, Giovanni D'Angelo, Josée Hébert and Guy Sauvageau

Key points

  • EVI1-r AMLs have recurrent mutations in RAS and other signaling genes, splicing factors and, at a lower frequency, IKZF1 and TP53.

  • EVI1-r AMLs show a characteristic transcriptome profile marked by high expression of MECOM, PREX2, MYCT1, PAWR and VIP.


The genetic and transcriptional signature of EVI1-rearranged (EVI1-r) acute myeloid leukemias (AMLs) remains poorly defined. We performed RNA-sequencing of 12 EVI1-r AMLs and compared the results to that 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) and identify new recurrent mutations in splicing factors (5/12 in SF3B1 and 2/12 in U2AF1), IKZF1 (3/12), and TP53 (3/12). 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.

  • Submitted July 28, 2014.
  • Accepted October 8, 2014.