A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth
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Meacham-2015-A genome-scale in vi.pdf
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Author(s) • • • • • • • • •
Meacham, Corbin Elizabeth
Lawton, Lee N.
Pritchard, Justin R.
Ehrenberger, Tobias
Fenouille, Nina
Zuber, Johannes
Williams, Richard T.
Young, Richard A.
Soto Feliciano, Yadira Marie
Hemann, Michael
Date Issued
March 2015
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
Meacham, Corbin E., Lee N. Lawton, Yadira M. Soto-Feliciano, Justin R. Pritchard, Brian A. Joughin, Tobias Ehrenberger, Nina Fenouille, et al. “A Genome-Scale in Vivo Loss-of-Function Screen Identifies Phf6 as a Lineage-Specific Regulator of Leukemia Cell Growth.” Genes Dev. 29, no. 5 (March 1, 2015): 483–488.
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Final published version
Abstract
We performed a genome-scale shRNA screen for modulators of B-cell leukemia progression in vivo. Results from this work revealed dramatic distinctions between the relative effects of shRNAs on the growth of tumor cells in culture versus in their native microenvironment. Specifically, we identified many “context-specific” regulators of leukemia development. These included the gene encoding the zinc finger protein Phf6. While inactivating mutations in PHF6 are commonly observed in human myeloid and T-cell malignancies, we found that Phf6 suppression in B-cell malignancies impairs tumor progression. Thus, Phf6 is a “lineage-specific” cancer gene that plays opposing roles in developmentally distinct hematopoietic malignancies.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1101/gad.254151.114