title: EVI1-rearranged acute myeloid leukemias are characterized by distinct molecular alterations.
abstract: 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.
authors.affiliation: The Leucegene Project at the Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada; Division of Hematology, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada;
authors.forename: Vincent-Philippe
authors.initials: VP
authors.lastname: Lavallée
authors.affiliation: The Leucegene Project at the Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada;
authors.forename: Patrick
authors.initials: P
authors.lastname: Gendron
authors.affiliation: The Leucegene Project at the Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada; Computer Science and Operation Research, Université de Montréal, Montréal, QC, Canada;
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lemieux
authors.affiliation: Banque de Cellules Leucémiques du Québec, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada; and.
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Angelo
authors.affiliation: The Leucegene Project at the Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada; Division of Hematology, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada; Banque de Cellules Leucémiques du Québec, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada; and Department of Medicine, Faculty of Medicine, Université de Montréal, QC, Canada.
authors.forename: Josée
authors.initials: J
authors.lastname: Hébert
authors.affiliation: The Leucegene Project at the Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada; Division of Hematology, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada; Banque de Cellules Leucémiques du Québec, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada; and Department of Medicine, Faculty of Medicine, Université de Montréal, QC, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Sauvageau
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D000074008:MDS1 and EVI1 Complex Locus Protein; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C497239:IKZF1 protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C477074:MYCT1 protein, human; D009687:Nuclear Proteins; C490712:PREX2 protein, human; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C101296:prostate apoptosis response-4 protein; D051740:Ikaros Transcription Factor; D014660:Vasoactive Intestinal Peptide