An Altered Microenvironment Within The Spleens Of Patients With Myelofibrosis Affects Cd34+Cell Trafficking

We have demonstrated that the homing of peripheral blood (PB) myelofibrosis (MF) CD34+ cells to the marrow but not the spleen is altered (Wang X, et al. Cancer Res. 2009;69:7612-8). The defective homing to the marrow was further found to be associated with both the down-regulation of CXCR4 expression by PB MF CD34+ cells (Wang X, et al. Cancer Res. 2009;69:7612-8) and the proteolytic degradation of CXCL12 in the plasma of MF patients (Cho SY, et al. Cancer Res. 2010;70:3402-10). However, the mechanism underlying the preferential homing, retention and engraftment of the MF HSCs/HPCs to extramedullary sites has not been clarified. Cancer stem cell behavior is thought to be determined by both intrinsic properties and by regulatory signals provided by the microenvironment. The effect of alterations within the splenic microenvironment on the trafficking of MF-stem cells (MF-SC) was, therefore, investigated.