Journal
GENES & DEVELOPMENT
Volume 29, Issue 5, Pages 483-488Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.254151.114
Keywords
Phf6; context dependency; in vivo screen; leukemia
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Funding
- Massachusetts Institute of Technology Department of Biology training grant
- Integrative Cancer Biology Program [U54-CA112967-06]
- National Institutes of Health [RO1-CA128803-05]
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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.
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