A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth
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; Joughin, Brian Alan; ... Show more Show less
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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.
DepartmentMassachusetts 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
Genes & Development
Cold Spring Harbor Laboratory Press
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.
Final published version