Title of article
Cell of Origin in AML: Susceptibility to MN1-Induced Transformation Is Regulated by the MEIS1/AbdB-like HOX Protein Complex
Author/Authors
Heuser، نويسنده , , Michael and Yun، نويسنده , , Haiyang and Berg، نويسنده , , Tobias and Yung، نويسنده , , Eric and Argiropoulos، نويسنده , , Bob and Kuchenbauer، نويسنده , , Florian and Park، نويسنده , , Gyeongsin and Hamwi، نويسنده , , Iyas and Palmqvist، نويسنده , , Lars and Lai، نويسنده , , Courteney K. and Leung، نويسنده , , Malina and Lin، نويسنده , , Grace and Chaturvedi، نويسنده , , Anuhar and Thakur، نويسنده , , Basant Kumar and Iwasaki، نويسنده , , Masayuki and Bilenky، نويسنده , , Mikhail and Thiessen، نويسنده , , Nina and Robertson، نويسنده , , Gordon and Hirst، نويسنده , , Martin and Kent، نويسنده , , David and Wilson، نويسنده , , Nicola K. and Gِttgens، نويسنده , , Bertie and Eaves، نويسنده , , Connie and Cleary، نويسنده , , Michael L. and Marra، نويسنده , , Marco and Ganser، نويسنده , , Arnold and Humphries، نويسنده , , R. Keith، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2011
Pages
14
From page
39
To page
52
Abstract
Summary
ys defining susceptibility of normal cells to oncogenic transformation may be valuable therapeutic targets. We characterized the cell of origin and its critical pathways in MN1-induced leukemias. Common myeloid (CMP) but not granulocyte-macrophage progenitors (GMP) could be transformed by MN1. Complementation studies of CMP-signature genes in GMPs demonstrated that MN1-leukemogenicity required the MEIS1/AbdB-like HOX-protein complex. ChIP-sequencing identified common target genes of MN1 and MEIS1 and demonstrated identical binding sites for a large proportion of their chromatin targets. Transcriptional repression of MEIS1 targets in established MN1 leukemias demonstrated antileukemic activity. As MN1 relies on but cannot activate expression of MEIS1/AbdB-like HOX proteins, transcriptional activity of these genes determines cellular susceptibility to MN1-induced transformation and may represent a promising therapeutic target.
lip
Journal title
Cancer Cell
Serial Year
2011
Journal title
Cancer Cell
Record number
1337558
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