A genome-scale in vivo loss-of-function screen identifies phf6 as a lineage-specific regulator of leukemia cell growth

Corbin E. Meacham, Lee N. Lawton, Yadira M. Soto-Feliciano, Justin R. Pritchard, Brian A. Joughin, Tobias Ehrenberger, Nina Fenouille, Johannes Zuber, Richard T. Williams, Richard A. Young, Michael T. Hemann

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)483-488
Number of pages6
JournalGenes and Development
Volume29
Issue number5
DOIs
StatePublished - Jan 1 2015

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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    Meacham, C. E., Lawton, L. N., Soto-Feliciano, Y. M., Pritchard, J. R., Joughin, B. A., Ehrenberger, T., Fenouille, N., Zuber, J., Williams, R. T., Young, R. A., & Hemann, M. T. (2015). A genome-scale in vivo loss-of-function screen identifies phf6 as a lineage-specific regulator of leukemia cell growth. Genes and Development, 29(5), 483-488. https://doi.org/10.1101/gad.254151.114