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Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Mol+Cell+Oncol 2015 ; 2 (3): ä Nephropedia Template TP
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Cutting the brakes on hematopoietic regeneration by blocking TGF? to limit chemotherapy-induced myelosuppression #MMPMID27308454
Brenet F; Scandura JM
Mol Cell Oncol 2015[Jul]; 2 (3): ä PMID27308454show ga
Hematopoietic stressors such as infection, bleeding, or toxic injury trigger a hematopoietic adaptation that sacrifices hematopoietic stem and progenitor cell (HSPC) quiescence to meet an urgent need for new blood cell production. Once the hematopoietic demands are adequately met, homeostasis must be restored. Transforming growth factor ? (TGF?) signaling is a central mediator mandating the return of HSPCs to quiescence after stress. Blockade of TGF? signaling after hematopoietic stress delays the return of cycling HSPCs to quiescence and in so doing promotes hematopoietic stem cell (HSC) self-renewal and accelerates hematopoietic reconstitution. These findings open the door to new therapeutics that modulate the hematopoietic adaptation to stress. In this review, we will discuss the complex context-dependent activities of TGF? in hematopoiesis and the potential benefits and limitations of using TGF? pathway inhibitors to promote multilineage hematopoietic reconstitution after myelosuppressive chemotherapy.