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

Lavallée VP, Gendron P, Lemieux S, D'Angelo G, Hébert J, Sauvageau G

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;

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.

Blood 2015;125(1):140-3.

Pubmed ID: 25331116

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