Abstract
Rearrangements of the mixed lineage leukemia gene MLL are associated with aggressive lymphoid and myeloid leukemias. The resulting MLL fusion proteins enforce high-level expression of HOX genes and the HOX cofactor MEIS1, which is pivotal for leukemogenesis. Both wild-type MLL and MLL fusion proteins interact with the tumor suppressor menin and with the Hoxa9 locus in vivo. Here, we show that MLL sequences between amino acids 5 and 44 are required for interaction with menin and for the transformation of hematopoietic progenitors. Blocking the MLL-menin interaction by the expression of a dominant negative inhibitor composed of amino terminal MLL sequences down-regulates Meis1 expression and inhibits cell proliferation, suggesting that targeting this interaction may be an effective therapeutic strategy for leukemias with MLL rearrangements.
Original language | English (US) |
---|---|
Pages (from-to) | 7275-7283 |
Number of pages | 9 |
Journal | Cancer Research |
Volume | 67 |
Issue number | 15 |
DOIs | |
State | Published - Aug 1 2007 |
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research