TY - JOUR
T1 - The genome-wide molecular signature of transcription factors in leukemia
AU - Prange, Koen H.M.
AU - Singh, Abhishek A.
AU - Martens, Joost H.A.
N1 - Funding Information: Work in our laboratory is supported by the Dutch Cancer Foundation ( KWF KUN 2009-4527 and KUN 2011-4937 ) and the Netherlands Organization for Scientific Research (NWO-VIDI 91711322 to JM).
PY - 2014/8
Y1 - 2014/8
N2 - Transcription factors control expression of genes essential for the normal functioning of the hematopoietic system and regulate development of distinct blood cell types. During leukemogenesis, aberrant regulation of transcription factors such as RUNX1, CBFβ, MLL, C/EBPα, SPI1, GATA, and TAL1 is central to the disease. Here, we will discuss the mechanisms of transcription factor deregulation in leukemia and how in recent years next-generation sequencing approaches have helped to elucidate the molecular role of many of these aberrantly expressed transcription factors. We will focus on the complexes in which these factors reside, the role of posttranslational modification of these factors, their involvement in setting up higher order chromatin structures, and their influence on the local epigenetic environment. We suggest that only comprehensive knowledge on all these aspects will increase our understanding of aberrant gene expression in leukemia as well as open new entry points for therapeutic intervention.
AB - Transcription factors control expression of genes essential for the normal functioning of the hematopoietic system and regulate development of distinct blood cell types. During leukemogenesis, aberrant regulation of transcription factors such as RUNX1, CBFβ, MLL, C/EBPα, SPI1, GATA, and TAL1 is central to the disease. Here, we will discuss the mechanisms of transcription factor deregulation in leukemia and how in recent years next-generation sequencing approaches have helped to elucidate the molecular role of many of these aberrantly expressed transcription factors. We will focus on the complexes in which these factors reside, the role of posttranslational modification of these factors, their involvement in setting up higher order chromatin structures, and their influence on the local epigenetic environment. We suggest that only comprehensive knowledge on all these aspects will increase our understanding of aberrant gene expression in leukemia as well as open new entry points for therapeutic intervention.
UR - http://www.scopus.com/inward/record.url?scp=84905161795&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.exphem.2014.04.012
DO - https://doi.org/10.1016/j.exphem.2014.04.012
M3 - Review article
C2 - 24814246
SN - 0301-472X
VL - 42
SP - 637
EP - 650
JO - Experimental Hematology
JF - Experimental Hematology
IS - 8
ER -