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Original Article

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Blood Res 2018; 53(1):

Published online March 31, 2018

https://doi.org/10.5045/br.2018.53.1.61

© The Korean Society of Hematology

Expression of adhesion molecules on CD34+ cells from steady-state bone marrow before and after mobilization and their association with the yield of CD34+ cells

Karin Zattar Cecyn*, Eliza Y.S. Kimura, Dulce Marta S.M. Lima, Miyoko Yamamoto, José Orlando Bordin, and José Salvador R. de Oliveira

Author Info. +

Oncologia Clínica e Experimental, Universidade Federal de São Paulo – UNIFESP, Sao Paulo, Brazil.

Correspondence to : Karin Zattar Cecyn, Ph.D. Oncologia Clínica e Experimental, Universidade Federal de São Paulo – UNIFESP, Rua Diogo de Faria-824, Vila Clementino, Sao Paulo, Brazil. kcecyn@gmail.com

Received: May 24, 2017; Revised: October 30, 2017; Accepted: December 14, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background

Cell adhesion molecules (CAMs) expressed on hematopoietic progenitor cells (HPCs), endothelial cells, and stromal cells play a pivotal role in the mobilization of CD34+ cells. Herein, we conducted a non-randomized peripheral blood stem cell (PBSC) mobilization study aimed to compare the potential differences in the expressions of several CAMs and chemokines on CD34+ cells obtained from bone marrow aspirate before and after HPC mobilization from patients with hematologic malignancies and healthy donors.

Methods

Three-color cytofluorometric analysis was used to compare the expressions of CAMs and chemokines in the bone marrow before and after mobilization.

Results

For all studied groups, CAM expression among those with good and poor yields of CD34+ cells was significantly correlated with VCAM-1 (P=0.007), CD44 (P=0.027), and VLA-4 (P=0.014) expressions. VCAM-1 (P=0.001), FLT-3 (P=0.001), CD44 (P=0.011), VLA-4 (P=0.001), and LFA-1 (P=0.001) expressions were higher before HPC mobilization than after HPC mobilization. By contrast, the expression of CXCR4 significantly varied before and after mobilization only among those with successful PBSC mobilization (P=0.002).

Conclusion

We attempted to identify particular aspects of CAMs involved in CD34+ cell mobilization, which is a highly complex mechanism that involves adhesion molecules and matrix metalloproteases. The mechanism by which CD34+ cell mobilization is activated through proteolytic enzymes is not fully understood. We believe that CXCR4, VLA-4, CD44, and VCAM-1 are the most important molecules implicated in HPC mobilization, particularly because they show a correlation with the yield of CD34+ cells collected via large volume leukapheresis.

Keywords Adhesion molecules, Hematopoietic progenitor cells, Mobilization, Stem cell donor, Multiple myeloma, Non-Hodgkin lymphoma

Article

Original Article

Blood Res 2018; 53(1): 61-70

Published online March 31, 2018 https://doi.org/10.5045/br.2018.53.1.61

Copyright © The Korean Society of Hematology.

Expression of adhesion molecules on CD34+ cells from steady-state bone marrow before and after mobilization and their association with the yield of CD34+ cells

Karin Zattar Cecyn*, Eliza Y.S. Kimura, Dulce Marta S.M. Lima, Miyoko Yamamoto, José Orlando Bordin, and José Salvador R. de Oliveira

Oncologia Clínica e Experimental, Universidade Federal de São Paulo – UNIFESP, Sao Paulo, Brazil.

Correspondence to:Karin Zattar Cecyn, Ph.D. Oncologia Clínica e Experimental, Universidade Federal de São Paulo – UNIFESP, Rua Diogo de Faria-824, Vila Clementino, Sao Paulo, Brazil. kcecyn@gmail.com

Received: May 24, 2017; Revised: October 30, 2017; Accepted: December 14, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Cell adhesion molecules (CAMs) expressed on hematopoietic progenitor cells (HPCs), endothelial cells, and stromal cells play a pivotal role in the mobilization of CD34+ cells. Herein, we conducted a non-randomized peripheral blood stem cell (PBSC) mobilization study aimed to compare the potential differences in the expressions of several CAMs and chemokines on CD34+ cells obtained from bone marrow aspirate before and after HPC mobilization from patients with hematologic malignancies and healthy donors.

Methods

Three-color cytofluorometric analysis was used to compare the expressions of CAMs and chemokines in the bone marrow before and after mobilization.

Results

For all studied groups, CAM expression among those with good and poor yields of CD34+ cells was significantly correlated with VCAM-1 (P=0.007), CD44 (P=0.027), and VLA-4 (P=0.014) expressions. VCAM-1 (P=0.001), FLT-3 (P=0.001), CD44 (P=0.011), VLA-4 (P=0.001), and LFA-1 (P=0.001) expressions were higher before HPC mobilization than after HPC mobilization. By contrast, the expression of CXCR4 significantly varied before and after mobilization only among those with successful PBSC mobilization (P=0.002).

Conclusion

We attempted to identify particular aspects of CAMs involved in CD34+ cell mobilization, which is a highly complex mechanism that involves adhesion molecules and matrix metalloproteases. The mechanism by which CD34+ cell mobilization is activated through proteolytic enzymes is not fully understood. We believe that CXCR4, VLA-4, CD44, and VCAM-1 are the most important molecules implicated in HPC mobilization, particularly because they show a correlation with the yield of CD34+ cells collected via large volume leukapheresis.

Keywords: Adhesion molecules, Hematopoietic progenitor cells, Mobilization, Stem cell donor, Multiple myeloma, Non-Hodgkin lymphoma

Fig 1.

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Figure 1.

Representative flow cytometric scattergrams from bone marrow aspirate specimens after HPC mobilization showing a 3-color cytofluorometric analysis of the expression of adhesion molecule antigens on CD34+ cells population. (A) CD34+ cells are painted in the lympho-mononuclear region. (B) CD34PE+ cells are included in R1 in the FSC/SSC dot plot. (C) CD34PE+ cells population in R2. (D) CD34FITC+ cells are included in R1 in the FSC/SSC dot plot. (E) CD34FITC+ cells population in R3. (F) CD34PE+ cells are included in R6 in the CD45PerCP/SSC dot plot. (G) CD34FITC+ cells are included in R6 in the CD45PerCP/SSC dot plot.

Blood Research 2018; 53: 61-70https://doi.org/10.5045/br.2018.53.1.61

Fig 2.

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Figure 2.

Representative flow cytometric histograms from bone marrow aspirate specimens after HPC mobilization showing a 3-color cytofluorometric analysis of the expression of adhesion molecule antigen on CD34+ cell population. The results were estimated as the mean fluorescence intensity (MFI). The histograms (A) and (B) are IgG1 FITC and PE controls. (C) CD106, (D) CD135, (E) CD184, (F) CD62L, (G) CD49d, (H) CD11a, and (I) CD44 antigen on CD34+ cell population. The gating protocols have been described before.

Blood Research 2018; 53: 61-70https://doi.org/10.5045/br.2018.53.1.61

Fig 3.

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Figure 3.

The mean expression of CD106, CD-44, and CD49d on the CD34+ cells assessed in BMA before mobilization and its association with the yield of CD34+ cells collected via LVL in both donors and patients.

Blood Research 2018; 53: 61-70https://doi.org/10.5045/br.2018.53.1.61

Fig 4.

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Figure 4.

Distribution of CD106, CD135, CD11a, CD44, CD49d, and CD184 assessed in mononuclear cells of the BMA, before and after mobilization according to the yield of CD34+ cells obtained via LGV.

Blood Research 2018; 53: 61-70https://doi.org/10.5045/br.2018.53.1.61

Fig 5.

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Figure 5.

Results obtained through logistic regression analysis. The chance of poor mobilization increases by approximately 6% with each increase of one unit of CD49d and by approximately 4% with each increase of one unit of CD44 in the pre-mobilization phase.

Blood Research 2018; 53: 61-70https://doi.org/10.5045/br.2018.53.1.61

Table 1 . Characteristics of the patients and donors..

PBPC, peripheral blood progenitors cells..

G-CSF, granulocyte-colony stimulating factor (10 µg/kg/day); Cy-Cyclophosphamide (5 g/m2); Cy+VP-16 Cyclophosphamide (5 g/m2)+VP-16 (400 mg/m2)..

ICE, Ifosfamide 5,000 mg/m2 carboplatin AUC=5 (max. 800 mg); e, 100 mg/m2..

DHAP, Cisplatin 100 mg/m2; cytarabine, 2,000 mg/m2; Dexamethasone 40 mg..

Table 2 . Mobilization and collection efficacy..

Abbreviations: LGV, lymphogranuloma venereum workup; LVL, large-volume leukapheresis; MM, multiple myeloma; NHL, non-Hodgkin's lymphoma; NL, Hodgkin's lymphoma..

Table 3 . Characteristics of patients who underwent large volume leukapheresis..

Abbreviations: ACD-A, acid-citrate-dextrose; CVC, central vein catheter; Hb, hemoglobin; LV, large volume leukapheresis; PL, platelets; WBC, white blood cells..

Table 4 . Comparative analysis of CAM expression assessed in BMA before and after HPC mobilization, considering good and poor yield of CD34+ cells in LVL. The expression of CD106, CD135, CD44, CD49d, and CD11a varied before and after mobilization, and this was independent of good CD34+ cell yield. Meanwhile, CD184 expression before and after mobilization was only different among those with a good yield of CD34+ cells (P=0.002)..


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