Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia.

Published

Journal Article

A subgroup of leukemogenic mixed-lineage leukemia (MLL) fusion proteins (MFPs) including MLL-AF9 activates the Mecom locus and exhibits extremely poor clinical prognosis. Mecom encodes EVI1 and MDS1-EVI1 (ME) proteins via alternative transcription start sites; these differ by the presence of a PRDI-BF1-RIZ1 (PR) domain with histone methyltransferase activity in the ME isoform. Using an ME-deficient mouse, we show that ME is required for MLL-AF9-induced transformation both in vitro and in vivo. And, although Nup98-HOXA9, MEIS1-HOXA9, and E2A-Hlf could transform ME-deficient cells, both MLL-AF9 and MLL-ENL were ineffective, indicating that the ME requirement is specific to MLL fusion leukemia. Further, we show that the PR domain is essential for MFP-induced transformation. These studies clearly indicate an essential role of PR-domain protein ME in MFP leukemia, suggesting that ME may be a novel target for therapeutic intervention for this group of leukemias.

Full Text

Duke Authors

Cited Authors

  • Zhang, Y; Owens, K; Hatem, L; Glass, CH; Karuppaiah, K; Camargo, F; Perkins, AS

Published Date

  • October 2013

Published In

Volume / Issue

  • 122 / 16

Start / End Page

  • 2888 - 2892

PubMed ID

  • 24021671

Pubmed Central ID

  • 24021671

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2012-08-453662

Language

  • eng