Levels of CD34+ progenitor cells mobilized into peripheral blood are associated with SDF1 Gene variants

Abstract Hematopoietic growth factors (GF) have greatly facilitated the mobilization and collection of peripheral blood (PB) stem cells. However, some patients fail to mobilize sufficient numbers of hematopoietic progenitor cells (HPC) to ensure rapid and durable engraftment. Interactions between the chemokine SDF-1 and its receptor CXCR4 have been shown to play a central role in the homing of HPC. To investigate a possible additional role of SDF-1 in the mobilization of CD34+ progenitor cells into PB, we examined the association of SDF1 gene polymorphism with circulating CD34+ cell counts after GF-priming. 63 patients (pts) were studied (48 malignant lymphoma, 8 myeloma and 7 solid tumors), after mobilization with G-CSF alone (n=11), chemotherapy (CT) and G-CSF (n=36) or GM-CSF (n=16). PB CD34+ cell counts were assessed when leukocytes reached 1,000/μl and graft collection performed when CD34+ counts reached 20/μl. The SDF1 3′G/A genotyping was performed on PB mononuclear cell DNA by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) which can detect the G to A mutation. Out of the 63 pts, 21 were able to mobilize 50 CD34+ cells/μl or more in PB. Their characteristics were not statistically different from others in terms of diagnosis, age, sex, number of previous CT courses, previous radiotherapy, marrow involvement or mobilizing regimens. Distribution of SDF1 genotypes in normal controls and in patients according to their mobilizing capacity was as follows: These results provide evidence for an association of the SDF1 3′A allele with more efficient mobilization of CD34+ progenitor cells into PB and suggest an involvement of SDF-1 in mobilization mechanisms.