Abstract
Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias.
Original language | English |
---|---|
Pages (from-to) | 597-608 |
Number of pages | 12 |
Journal | Cancer Cell |
Volume | 17 |
Issue number | 6 |
DOIs | |
Publication status | Published - Jun 15 2010 |
Keywords
- CELLCYCLE
ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Oncology