Imperial College London
Alternate

ProfessorJesusGil

Faculty of Medicine, Institute of Clinical Sciences

Professor of Cell Proliferation
 
 
 
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Contact

 

+44 (0)20 3313 8263jesus.gil

 
 
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Location

 

ICTEM room 230ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Smith:2011:10.1016/j.stem.2011.05.004,
author = {Smith, L-L and Yeung, J and Zeisig, BB and Popov, N and Huijbers, I and Barnes, J and Wilson, AJ and Taskesen, E and Delwel, R and Gil, J and Lohuizen, MV and So, CWE},
doi = {10.1016/j.stem.2011.05.004},
journal = {Cell stem cell},
pages = {649--62},
title = {Functional Crosstalk between Bmi1 and MLL/Hoxa9 Axis in Establishment of Normal Hematopoietic and Leukemic Stem Cells},
url = {http://dx.doi.org/10.1016/j.stem.2011.05.004},
volume = {8},
year = {2011}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bmi1 is required for efficient self-renewal of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). In this study, we investigated whether leukemia-associated fusion proteins, which differ in their ability to activate Hox expression, could initiate leukemia in the absence of Bmi1. AML1-ETO and PLZF-RARα, which do not activate Hox, triggered senescence in Bmi1(-/-) cells. In contrast, MLL-AF9, which drives expression of Hoxa7 and Hoxa9, readily transformed Bmi1(-/-) cells. MLL-AF9 could not initiate leukemia in Bmi1(-/-)Hoxa9(-/-) mice, which have further compromised HSC functions. But either gene could restore the ability of MLL-AF9 to establish LSCs in the double null background. As reported for Bmi1, Hoxa9 regulates expression of p16(Ink4a)/p19(ARF) locus and could overcome senescence induced by AML1-ETO. Together, these results reveal an important functional interplay between MLL/Hox and Bmi1 in regulating cellular senescence for LSC development, suggesting that a synergistic targeting of both molecules is required to eradicate a broader spectrum of LSCs.
AU  - Smith,L-L
AU  - Yeung,J
AU  - Zeisig,BB
AU  - Popov,N
AU  - Huijbers,I
AU  - Barnes,J
AU  - Wilson,AJ
AU  - Taskesen,E
AU  - Delwel,R
AU  - Gil,J
AU  - Lohuizen,MV
AU  - So,CWE
DO  - 10.1016/j.stem.2011.05.004
EP  - 62
PY  - 2011///
SP  - 649
TI  - Functional Crosstalk between Bmi1 and MLL/Hoxa9 Axis in Establishment of Normal Hematopoietic and Leukemic Stem Cells
T2  - Cell stem cell
UR  - http://dx.doi.org/10.1016/j.stem.2011.05.004
VL  - 8
ER  -
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