摘要
One of the major obstacles limiting the success of hematopoietic reconstitution appears to be the low efficiency of hematopoietic stem cell(HSC)engraftment in the recipient’s bone marrow.Among the key factors regulating the hematopoietic reconstitution,the stromal-derived factor-1(SDF-1)/chemokine receptor CXCR4 axis has long been known to be crucial due to its roles in HSC functions,such as homing/mobilization,engraftment,and quiescence.The SDF-1/CXCR4-mediated marrow engraftment processes have been mostly dissected through loss of function experiments involving SDF-1/CXCR4 signals.1 There have been no previously published reports indicating whether manipulation of the SDF-1/CXCR4 axis can lead to enhanced HSC engraftment in a competitive transplantation model using syngeneic mice.However,this notion is about to change in view of a recent discovery by a group of scientists from the NIH and several prominent universities.2 While studying one of the first reported cases of spontaneous remission of WHIM syndrome,a primary immunodeficiency disease caused by autosomal dominant gain-of-function CXCR4 mutations,this group of scientists,led by Dr.Philip Murphy,observed that the deletion of the mutant CXCR4 disease allele,together with another 163 genes from one copy of chromosome 2 in marrow HSC/progenitors.
