| First Author | Zhang Y | Year | 2013 |
| Journal | Blood | Volume | 122 |
| Issue | 16 | Pages | 2888-92 |
| PubMed ID | 24021671 | Mgi Jnum | J:204084 |
| Mgi Id | MGI:5529569 | Doi | 10.1182/blood-2012-08-453662 |
| Citation | Zhang Y, et al. (2013) Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia. Blood 122(16):2888-92 |
| abstractText | 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. |
