Title | A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Meacham, CE, Lawton, LN, Soto-Feliciano, YM, Pritchard, JR, Joughin, BA, Ehrenberger, T, Fenouille, N, Zuber, J, Williams, RT, Young, RA, Hemann, MT |
Journal | Genes Dev |
Volume | 29 |
Issue | 5 |
Pagination | 483-8 |
Date Published | 2015 Mar 1 |
ISSN | 1549-5477 |
Keywords | Carrier Proteins, Cell Lineage, Cell Proliferation, Genome, Human, Humans, Leukemia, Mutation, RNA, Small Interfering |
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. |
DOI | 10.1101/gad.254151.114 |
Alternate Journal | Genes Dev. |
PubMed ID | 25737277 |
PubMed Central ID | PMC4358400 |
Grant List | P30 CA014051 / CA / NCI NIH HHS / United States R01-CA128803-05 / CA / NCI NIH HHS / United States T32 GM007287 / GM / NIGMS NIH HHS / United States U54-CA112967-06 / CA / NCI NIH HHS / United States |