Transgenic bcl-2 is not sufficient to rescue all hematolymphoid defects in STAT5A/5B-deficient mice.
OBJECTIVE
Cytokines bind high-affinity receptors expressed on hematopoietic cells to initiate signaling cascades that regulate differentiation, proliferation, and survival. Previous studies have established a role for STAT5 in transducing survival signals for hematopoietic progenitor cells in response to cytokines.


METHODS
To determine if constitutive expression of a member of the bcl-2 family of anti-apoptotic proteins could compensate for the loss of STAT5, we utilized combinatorial genetics to generate STAT5A/5B-deficient mice expressing a bcl-2 transgene.


RESULTS
Although bcl-2 expression restored peripheral blood counts to normal in STAT5A/5B(-/-) mice, we noted a striking failure of this transgene to correct defects in hematopoietic stem and progenitor cells.


CONCLUSIONS
These data imply important effects of STAT5 in modulating hematopoietic cells in addition to promoting survival per se.
Snow
Jonathan W
JW
Gladstone Institute of Virology and Immunology, Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94141-9100, USA.
Abraham
Ninan
N
Ma
Melissa C
MC
Bronson
Sarah K
SK
Goldsmith
Mark A
MA
D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006413:Hematopoietic System / Q000187:drug effects* / Q000254:growth & development; D008208:Lymphatic System / Q000187:drug effects* / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D019076:Transgenes; D017211:Treatment Failure
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators