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. Materials and 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. Conclusion These data imply important effects of STAT5 in modulating hematopoietic cells in addition to promoting survival per se.