First Author | Chen Y | Year | 2017 |
Journal | Cancer Cell | Volume | 31 |
Issue | 6 | Pages | 755-770.e6 |
PubMed ID | 28609655 | Mgi Jnum | J:242562 |
Mgi Id | MGI:5905672 | Doi | 10.1016/j.ccell.2017.05.002 |
Citation | Chen Y, et al. (2017) MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia. Cancer Cell 31(6):755-770.e6 |
abstractText | The MLL1 histone methyltransferase gene undergoes many distinct chromosomal rearrangements to yield poor-prognosis leukemia. The remaining wild-type allele is most commonly, but not always, retained. To what extent the wild-type allele contributes to leukemogenesis is unclear. Here we show, using rigorous, independent animal models, that endogenous MLL1 is dispensable for MLL-rearranged leukemia. Potential redundancy was addressed by co-deleting the closest paralog, Mll2. Surprisingly, Mll2 deletion alone had a significant impact on survival of MLL-AF9-transformed cells, and additional Mll1 loss further reduced viability and proliferation. We show that MLL1/MLL2 collaboration is not through redundancy, but regulation of distinct pathways. These findings highlight the relevance of MLL2 as a drug target in MLL-rearranged leukemia and suggest its broader significance in AML. |