CXCR4 expression on transplanted peripheral blood CD34+ cells: relationship to engraftment after autologous transplantation in a cohort of multiple myeloma patients

Abstract

Expression of the chemokine receptor CXCR4 by haematopoietic stem cells (HSCs) is believed to influence the process of these cells 'homing' back to the bone marrow post-transplantation, in response to the stromal cell-derived factor-1 gradient, followed by engraftment. The primary aim of this retrospective study was to compare reinfused CD34(+) cell dose, assessed from the fresh collection, with the post-thaw viable (v) CD34(+) and vCD34/CXCR4(+) dual positive cell dose as predictors of haematopoietic recovery in multiple myeloma patients undergoing autologous stem cell transplantation. Cryopreserved samples from stem cell collections of 27 myeloma patients were analysed for CD34 and CXCR4 expression and times to haematological engraftment measured. Dosage of transplanted vCD34(+) cells was on average 79% of the original calculation from the fresh collection bag (range 29-98%). The median percentage of vCD34+ cells co-expressing CXCR4 was 37% (3.7-97%). Surface expression of CXCR4 by thawed vCD34(+) cells was closely correlated to complementary DNA levels. The median dose of CD34/CXCR4(+) cells in the autografts was 1.2 × 10(6)/kg (0.2-3.0 × 10(6)/kg) compared with 3.3 × 10(6)/kg for transplanted vCD34(+) cells (1.2-5.5 × 10(6)/kg). Both CD34 and vCD34 doses correlated with neutrophil engraftment (p < 0.005) although vCD34/CXCR4(+) dose did not. However, patients given a higher dose of CD34/CXCR4(+) cells (≥1.75 × 10(6)/kg) showed a faster time to platelet recovery (p < 0.05) than those given a lower dose (≤0.42 × 10(6)/kg). These results warrant further study of CD34/CXCR4 expression by mobilised HSCs and the relationship to platelet recovery post-transplantation on a larger cohort of patients.

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

“…Conversely, CXCR4 expression in both mice and human cells correlated positively with autologous and xeno-engraftment [120,121]. In humans, following G-CSF mobilization, CXCR4 expression showed a positive correlation with engraftment [122,123,124]. Surprisingly, here, the CXCL12 3’UTR A polymorphism whose occurrence had been associated with increased mobilization (see the Mobilization subsection) was associated with faster hematopoietic recovery in autologous transplant patients [125].…”

CD31 expression on peripheral blood stem cells predicts both early neutrophil and platelet engraftments

“…In several studies with small sample sizes, it has been concluded that the expression of CD184 (CXCR4) on HSCs served to influence the 'homing' process of these cells back to the bone marrow, as a response to CXCL12, followed by engraftment [1,2,18,19]. Recently, in a retrospective study, Hicks et al [2] have shown that higher doses of CD34/ CXCR4+ cells (P1.75 Â 10 6 /kg) results in a faster time to platelet recovery than lower doses (60.42 Â 10 6 /kg) in 27 patients. In contrast, in this prospective study, containing relatively more patients/donors, we concluded that the CD184 (CXCR4) expression ratio and even CD184 negativity (Figs.…”

“…Several protein interactions help to anchor HSCs within the bone marrow, including the chemokine receptor CXC motif receptor 4 (CXCR4, or CD184) and its ligand CXCL12 (previously named stromal cell-derived factor-1), CD44/hyaluronic acid, c-kit/kit ligand, very late antigen-4/vascular cell adhesion molecule-1, and CD62/ CD62L [1]. The processes of progenitor cell egress from their specialized bone marrow niche (mobilization) and trafficking from the peripheral blood back to the marrow microenvironment (homing) can be considered as mirror images of each other and are mediated by these proteins [1,2].…”

“…Most HSCs remain tethered to the bone marrow through adhesion molecule/receptor interactions with bone marrow stromal cells, osteoblasts, and osteoclasts [1][2][3]. Several protein interactions help to anchor HSCs within the bone marrow, including the chemokine receptor CXC motif receptor 4 (CXCR4, or CD184) and its ligand CXCL12 (previously named stromal cell-derived factor-1), CD44/hyaluronic acid, c-kit/kit ligand, very late antigen-4/vascular cell adhesion molecule-1, and CD62/ CD62L [1].…”

Granulocyte–Colony Stimulating Factor plus Plerixafor in Patients with β-thalassemia Major Results in the Effective Mobilization of Primitive CD34+ Cells with Specific Gene Expression Profile

“…28 CXCR4 is expressed on the surface of HSPCs, especially more primitive CD34+ cells with long-term repopulating potential, and it plays a central role in regulating the adhesion of HSPCs to their native niche in BM. 31 Conversely, genes involved in the cleavage of VCAM-1 and SDF-1 (CXCL12) antigens, such as elastase (ELANE) and cathepsin G (CTSG), were overexpressed in both CD34/G+pl and CD34/G cells. These data are in line with a mechanism involving G-CSF mobilization.…”