A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth.

Autor:	Meacham CE; The Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;, Lawton LN; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA;, Soto-Feliciano YM; The Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;, Pritchard JR; The Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;, Joughin BA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;, Ehrenberger T; The Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;, Fenouille N; The Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;, Zuber J; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;, Williams RT; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA., Young RA; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA;, Hemann MT; The Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; hemann@mit.edu.
Jazyk:	angličtina
Zdroj:	Genes & development [Genes Dev] 2015 Mar 01; Vol. 29 (5), pp. 483-8.
DOI:	10.1101/gad.254151.114
Abstrakt:	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. (© 2015 Meacham et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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