Association between the SDF1‐3′A allele and high levels of CD34⁺ progenitor cells mobilized into peripheral blood in humans

Abstract

Summary. Some patients unexpectedly fail to mobilize sufficient numbers of haematopoietic progenitor cells (HPCs) into the peripheral blood for autologous transplantation. Considering the important role of the chemokine stromal cell-derived factor 1 (SDF-1) in HPC homing, we investigated a possible relationship between SDF1 gene polymorphism and HPC mobilization capacity in 63 patients with malignancy. Some 67% of the good mobilizers ($ 50 CD34 1 cells/ml) and only 36% of the intermediate/poor mobilizers were SDF1-3 0 A allele carriers (P 0´032). In multivariate analysis, the presence of the SDF1-3 0 A allele was the only factor predictive of good CD341 cell mobilization (P 0´025). This is the first report showing the involvement of genetic factors for HPC mobilization in humans and suggests a significant role for SDF-1 in this process.

The CXCL12-3′A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation

“…In addition, these results correspond with our observations in lymphoma patients (with either the GG or GA genotypes) who failed to have a sufficient number of CD34 þ cells for autologous transplantation, in spite of three leukaphereses performed (unpublished results). Thus, our results regarding patients undergoing autologous transplantation of haematopoietic stem cells concur with those reported by Benboubker et al 15 The association between the CXCL12 gene polymorphism and the serum levels of CXCL12vwas suggested by Winkler et al 11 However, to date, the exact relationship between the CXCL12 genotypes and the corresponding protein production is not clear and the studies examining the association differ in their methodological approaches. [20][21][22][23] As this mutation lies in the 3 0 UTR of the gene, Winkler et al 11 suggested that this mutation may upregulate transcription of the gene, resulting in more abundant CXCL12, which in turn, inhibits T-tropic HIV-1 and delays the onset of the disease.…”

“…Indeed, Benboubker et al 15 have demonstrated that the CXCL12 gene polymorphism may influence the egress of CD34 cells to the peripheral blood in patients mobilized for autologous transplantation. However, all of the patients analysed in that study received chemotherapy before, or during, mobilization that could affect the number of haematopoietic progenitors mobilized to peripheral blood.…”

“…13 Additionally, Christopherson et al 14 have demonstrated that the mechanism of action underlying the G-CSF-mobilization of haematopoietic stem cells in a murine system also involves the activity of CD26, an extracellular peptidase, suggesting that this process is more complex. Moreover, a study by Benboubker et al 15 has shown that the CXCL12 gene polymorphism may influence the egress of CD34 þ cells to the peripheral blood in patients mobilized for autologous transplantation.…”

Genetic control of chemokines in severe human internal carotid artery stenosis

“…Carriers of the A allele in the SDF-1 gene were at increased risk of developing ICA occlusive disease compared with individuals homozygous for the G. The -801A variant of the SDF-1 gene has been associated with genetic restriction of AIDS pathogenesis, as well as with enhanced CD34+ progenitor cell mobilisation from bone marrow [29,30]. Soriano et al have shown an association between high plasma SDF-1 levels and the SDF-1 A allele [31].…”

The SDF1-G801A polymorphism is not associated with SDF1 gene expression in Epstein–Barr virus-transformed lymphoblastoid cells

“…Besides the concern with AIDS progression, it has been suggested that the SDF1-3 0 A increases the levels of CD34 + progenitor cells mobilized into peripheral blood, 16 and has a relation with an early onset of type I diabetes. 17 Although the effects of the SDF1-3 0 A have been attributed to the alteration of the amount of SDF-1, participation of the polymorphism in SDF-1 expression SDFI-G801A and SDFI gene expression R Kimura et al has been still unclear and awaited to be revealed.…”