Imperial College London

ProfessorBorisLenhard

Faculty of MedicineInstitute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

+44 (0)20 3313 8353b.lenhard Website

 
 
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Assistant

 

Mr Alastair Douglas Ivor Williams +44 (0)20 3313 4318

 
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Location

 

230ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lenhard:2017:10.15252/embj.201797994,
author = {Lenhard, B and Siriboonpiputtana, T and So, CWE},
doi = {10.15252/embj.201797994},
journal = {EMBO Journal},
title = {Transcriptional memory of cells of origin overrides βcatenin requirement of MLL cancer stem cells},
url = {http://dx.doi.org/10.15252/embj.201797994},
year = {2017}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - While βcatenin has been demonstrated as an essential molecule and therapeutic target for various cancer stem cells (CSCs) including those driven by MLL fusions, here we show that transcriptional memory from cells of origin predicts AML patient survival and allows βcateninindependent transformation in MLLCSCs derived from hematopoietic stem cell (HSC)enriched LSK population but not myeloid–granulocyte progenitors. Mechanistically, βcatenin regulates expression of downstream targets of a key transcriptional memory gene, Hoxa9 that is highly enriched in LSKderived MLLCSCs and helps sustain leukemic selfrenewal. Suppression of Hoxa9 sensitizes LSKderived MLLCSCs to βcatenin inhibition resulting in abolishment of CSC transcriptional program and transformation ability. In addition, further molecular and functional analyses identified Prmt1 as a key common downstream mediator for βcatenin/Hoxa9 functions in LSKderived MLLCSCs. Together, these findings not only uncover an unexpectedly important role of cells of origin transcriptional memory in regulating CSC selfrenewal, but also reveal a novel molecular network mediated by βcatenin/Hoxa9/Prmt1 in governing leukemic selfrenewal.
AU - Lenhard,B
AU - Siriboonpiputtana,T
AU - So,CWE
DO - 10.15252/embj.201797994
PY - 2017///
SN - 0261-4189
TI - Transcriptional memory of cells of origin overrides βcatenin requirement of MLL cancer stem cells
T2 - EMBO Journal
UR - http://dx.doi.org/10.15252/embj.201797994
ER -