| Literature DB >> 27846391 |
Shan Lin1, Roger T Luo2, Anetta Ptasinska3, Jon Kerry4, Salam A Assi3, Mark Wunderlich1, Toshihiko Imamura2, Joseph J Kaberlein2, Ahmad Rayes1, Mark J Althoff1, John Anastasi5, Maureen M O'Brien1, Amom Ruhikanta Meetei1, Thomas A Milne4, Constanze Bonifer3, James C Mulloy6, Michael J Thirman7.
Abstract
The t(4;11)(q21;q23) fuses mixed-lineage leukemia (MLL) to AF4, the most common MLL-fusion partner. Here we show that MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34+ cells, thereby generating a model of t(4;11) pro-B acute lymphoblastic leukemia (ALL) that fully recapitulates the immunophenotypic and molecular aspects of the disease. MLL-Af4 induces a B ALL distinct from MLL-AF9 through differential genomic target binding of the fusion proteins leading to specific gene expression patterns. MLL-Af4 cells can assume a myeloid state under environmental pressure but retain lymphoid-lineage potential. Such incongruity was also observed in t(4;11) patients in whom leukemia evaded CD19-directed therapy by undergoing myeloid-lineage switch. Our model provides a valuable tool to unravel the pathogenesis of MLL-AF4 leukemogenesis.Entities:
Keywords: MLL-AF4; acquired resistance to targeted therapy; acute lymphoblastic leukemia; chimeric fusion proteins; mouse models of cancer; species specificity of oncogenes
Mesh：
Substances：
Year: 2016 PMID： 27846391 DOI： 10.1016/j.ccell.2016.10.008
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743