Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency

DSpace/Manakin Repository

Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency

Citable link to this page

 

 
Title: Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency
Author: Blackburn, Jessica S.; Liu, Sali; Raiser, Dave Michael; Martinez, Sarah A.; Feng, Hui; Meeker, Nathan D.; Gentry, Jeffery; Neuberg, Donna S.; Look, A. Thomas; Ramaswamy, Sridhar; Bernards, Andre; Trede, Nikolaus S.; Langenau, David M.

Note: Order does not necessarily reflect citation order of authors.

Citation: Blackburn, Jessica S., Sali Liu, David M. Raiser, Sarah A. Martinez, Hui Feng, Nathan D. Meeker, Jeffery Gentry, et al. 2012. Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency. Leukemia 26(9): 2069-2078.
Full Text & Related Files:
Abstract: NOTCH1 pathway activation contributes to the pathogenesis of over 60% of T-cell acute lymphoblastic leukemia (T-ALL). While Notch is thought to exert the majority of its effects through transcriptional activation of Myc, it also likely has independent roles in T-ALL malignancy. Here, we utilized a zebrafish transgenic model of T-ALL, where Notch does not induce Myc transcription, to identify a novel Notch gene expression signature that is also found in human T-ALL and is regulated independently of Myc. Cross-species microarray comparisons between zebrafish and mammalian disease identified a common T-ALL gene signature, suggesting that conserved genetic pathways underlie T-ALL development. Functionally, Notch expression induced a significant expansion of pre-leukemic clones; however, a majority of these clones were not fully transformed and could not induce leukemia when transplanted into recipient animals. Limiting-dilution cell transplantation revealed that Notch signaling does not increase the overall frequency of leukemia-propagating cells (LPCs), either alone or in collaboration with Myc. Taken together, these data indicate that a primary role of Notch signaling in T-ALL is to expand a population of pre-malignant thymocytes, of which a subset acquire the necessary mutations to become fully transformed LPCs.
Published Version: doi:10.1038/leu.2012.116
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435461/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10609670
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters