Expression of adhesion molecules on CD34+ cells: CD34+ L-selectin+ cells predict a rapid platelet recovery after peripheral blood stem cell transplantation

Abstract

Adhesion molecules play a role in the migration of hematopoietic progenitor cells and regulation of hematopoiesis. To study whether the mobilization process is associated with changes in expression of adhesion molecules, the expression of CD31, CD44, L-selectin, sialyl Lewisx, beta 1 integrins very late antigen 4 (VLA-4) and VLA-5, and beta 2 integrins lymphocyte function-associated 1 and Mac-1 was measured on either bone marrow (BM) CD34+ cells or on peripheral blood CD34+ cells mobilized with a combination of granulocyte colony-stimulating factor (G-CSF) and chemotherapy. beta 1 integrin VLA-4 was expressed at a significantly lower concentration on peripheral blood progenitor cells than on BM CD34+ cells, procured either during steady-state hematopoiesis or at the time of leukocytapheresis. No differences in the level of expression were found for the other adhesion molecules. To obtain insight in which adhesion molecules may participate in the homing of peripheral blood stem cells (PBSCs), the number of CD34+ cells expressing these adhesion molecules present in leukocytapheresis material was quantified and correlated with hematopoietic recovery after intensive chemotherapy in 27 patients. The number of CD34+ cells in the subset defined by L-selectin expression correlated significantly better with time to platelet recovery after PBSC transplantation (r = -.86) than did the total number of CD34+ cells (r = -.55). Statistical analysis of the relationship between the number of CD34+L-selectin+ cells and platelet recovery resulted in a threshold value for rapid platelet recovery of 2.1 x 10(6) CD34+ L-selectin+ cells/kg. A rapid platelet recovery (< or = 14 days) was observed in 13 of 15 patients who received > or = 2.1 x 10(6) CD34+ L-selectin+ cells/kg (median, 11 days; range, 7 to 16 days), whereas 10 of 12 patients who received less double positive cells had a relative slow platelet recovery (median, 20 days; range, 13 to 37 days). The L-selectin+ subpopulation of CD34+ cells also correlated better with time to neutrophil recovery (r = -.70) than did the total number of reinfused CD34+ cells (r = -.51). However, this latter difference failed to reach statistical significance. This study suggests that L-selectin is involved in the homing of CD34+ cells after PBSC transplantation.

Cryopreservation of cord blood CD34+ cells before or after thrombopoietin expansion differentially affects early platelet recovery in NOD SCID mice

“…Indeed, CD62L expression has been correlated to speed of hematopoietic recovery 30 and in particular with PLT recovery. 31 In this regard, the lower migration toward an SDF-1a gradient of the CD62L-population we observed seems compatible with previous reports. The lower number of CD62L-expressing cells derived from the ECT pathway might in this regard explain why fewer cells from the ECT pathway are able to migrate toward or within the marrow.…”

Granulocyte colony‐stimulating factor mobilized whole blood containing over 0·3 × 106/kg CD34+ cells is a sufficient graft in autologous transplantation for relapsed non‐Hodgkin's lymphoma

“…In addition, cryopreservation may effect the homing potential of stem cells. It has been shown that the expression of certain adhesion molecules and the in vitro migratory capacity of CD34 + cells are correlated with haematological recovery (Dercksen et al, 1995;Watanabe et al, 1998;Voermans et al, 2001). Comparison of adhesion molecule expression on WB CD34 + cells after 3 d of refrigerated storage with cryopreserved PBSC CD34 + cells revealed a 50% loss of l-selectin expression on the non-apoptotic CD34 + cells of the cryopreserved PBSC (De Boer et al, 2002b).…”

Delineation of Cell Cycle State and Correlation to Adhesion Molecule Expression of Human CD34+Cells from Steady‐State Bone Marrow and Peripheral Blood Mobilized Following G‐CSF‐Supported Chemotherapy

“…We were further interested whether cell cycle progression is linked to the expression of adhesion molecules. Antigens of the β 1 -integrin (CD49b, CD49d, CD49e), the β 2 -integrin (CD18), the selectin (CD62L), and the immunoglobulin (CD58) family that had previously been found on normal or leukemic hematopoietic progenitor cells [19][20][21] were included in this matchedpair steady-state BM and mobilized PB analysis. The highest proportion of CD34 + cells expressed CD49d, followed by CD49e and CD49b regarding β 1 -integrins (Table 3).…”

“…In previous experiments, we and others found a significantly greater fluorescence intensity of the adhesion molecule CD49d and the leukocyte function associated molecule-1 (LFA-1) complex which consists of the αL/β2 (CD11a/CD18) chains on BM CD34 + cells than with mobilized PBPC [17,18]. In this analysis also, CD49b, CD49e, CD58 (LFA-3), and CD62L (L-Selectin), which were all reported on CD34 + cells, were included [19][20][21]. Leukapheresis product samples were obtained from 14 patients with hematological malignancies and solid tumors following G-CSF-supported cytotoxic chemotherapy and were compared with BM cells obtained prior to mobilization from these patients with regard to cell biological and immunological progenitor cell subsets as well as cell cycle state.…”