Imperial College London
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DrAndrewInnes

Faculty of Medicine, Department of Immunology and Inflammation

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 4017a.innes

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cuartero:2019:10.3389/fonc.2019.00867,
author = {Cuartero, S and Innes, AJ and Merkenschlager, M},
doi = {10.3389/fonc.2019.00867},
journal = {Frontiers in Oncology},
title = {Towards a better understanding of cohesin mutations in AML},
url = {http://dx.doi.org/10.3389/fonc.2019.00867},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Classical driver mutations in acute myeloid leukemia (AML) typically affect regulatorsof cell proliferation, differentiation, and survival. The selective advantage of increasedproliferation, improved survival, and reduced differentiation on leukemia progression isimmediately obvious. Recent large-scale sequencing efforts have uncovered numerousnovel AML-associated mutations. Interestingly, a substantial fraction of the mostfrequently mutated genes encode general regulators of transcription and chromatinstate. Understanding the selective advantage conferred by these mutations remains amajor challenge. A striking example are mutations in genes of the cohesin complex,a major regulator of three-dimensional genome organization. Several landmark studieshave shown that cohesin mutations perturb the balance between self-renewal anddifferentiation of hematopoietic stem and progenitor cells (HSPC). Emerging data nowbegin to uncover the molecular mechanisms that underpin this phenotype. Amongthese mechanisms is a role for cohesin in the control of inflammatory responses inHSPCs and myeloid cells. Inflammatory signals limit HSPC self-renewal and driveHSPC differentiation. Consistent with this, cohesin mutations promote resistance toinflammatory signals, and may provide a selective advantage for AML progression.In this review, we discuss recent progress in understanding cohesin mutations inAML, and speculate whether vulnerabilities associated with these mutations could beexploited therapeutically
AU  - Cuartero,S
AU  - Innes,AJ
AU  - Merkenschlager,M
DO  - 10.3389/fonc.2019.00867
PY  - 2019///
SN  - 2234-943X
TI  - Towards a better understanding of cohesin mutations in AML
T2  - Frontiers in Oncology
UR  - http://dx.doi.org/10.3389/fonc.2019.00867
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000484970800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/73631
VL  - 9
ER  -
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