Notch2 blockade enhances hematopoietic stem cell mobilization and homing.

Notch2 blockade enhances hematopoietic stem cell mobilization and homing. Haematologica. 2017 Jul 20;: Authors: Wang W, Yu S, Myers J, Wang Y, Xin WW, Alkabri M, Xin AW, Li M, Huang AY, Xin W, Siebel CW, Lazarus HM, Zhou L Abstract Despite use of newer approaches, some patients being considered for autologous hematopoietic cell transplantation may mobilize limited numbers of hematopoietic progenitor cells into blood, precluding use of the procedure, or being placed at increased risk for complications due to slow hematopoietic reconstitution. Developing more efficacious hematopoietic progenitor cell mobilization regimens and strategies may enhance the mobilization process and improve patient outcome. Although Notch signaling is dispensable for homeostasis of adult hematopoietic stem cells, Notch-ligand adhesive interaction maintains hematopoietic stem cell quiescence and niche retention. Using Notch receptor blocking antibodies, we report that Notch2 blockade but not Notch1 blockade sensitizes hematopoietic stem cell and progenitors to mobilization stimuli and leads to enhanced egress from marrow to the periphery. Notch2 blockade leads to transient myeloid progenitor expansion without affecting hematopoietic stem cell homeostasis and self-renewal. We show that transient Notch2 blockade or Notch2-loss in mice lacking Notch2 receptor leads to decreased CXCR4 expression by hematopoietic stem cell but increased cell cycling with CXCR4 tra...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research