Expression of the Chemokine Receptors CXCR4 and CCR7 and Disease Progression in B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Irene M. Ghobrial, Nancy D. Bone, Mary J. Stenson, Anne J Novak, Karen Elaine Hedin, Neil Elliot Kay, Stephen Maxted Ansell

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Abstract

Objective: To assess the clinical relevance of chemokine receptor expression on the progression of B-cell chronic lymphocytic leukemia (B-CLL). Patients and Methods: Peripheral blood mononuclear cells from 45 patients with B-CLL were purified and compared with lymph node samples collected from 17 of these patients. Also compared were B cells obtained from peripheral blood samples from 5 healthy controls and B cells from reactive lymph nodes from 3 otherwise healthy persons. The patients were treated at the Mayo Clinic in Rochester, Minn, between January 15, 1991, and February 7, 2003. Mononuclear cells were stained by a 2-color (fluorescein isothiocyanate/phycoerythrin) flow cytometric assay using antibodies to the chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CCR2, CCR4, CCR5, CCR6, and CCR7) and also to CD19. Results: Of the 45 patients in this study, 20 had Rai stage 0 disease, 12 had stage I disease, 3 had stage II disease, 2 had stage III disease, and 8 had stage IV disease. The mean fluorescent intensity (MFI) of the chemokine receptor expression on B-CLL cells was compared with normal controls and was not significantly different, except for an increase in the median expression of CXCR3 (P=.003) and CCR7 (P=.001) on B-CLL cells. We also found a significant increase in the expression of CXCR4 and CCR7 in B-CLL cells from patients with stage IV compared with stage 0 disease (P=.001 and P=.02, respectively). Furthermore, circulating B-CLL cells showed significantly higher expression of CXCR4 and CCR7 when compared with B lymphocytes in lymph nodes (P=.003 and P<.001, respectively). Conclusion: The expression of CXCR4 and CCR7 on B-CLL cells correlates with Rai stage. Also, these chemokine receptors may be down-regulated once malignant B cells enter the lymph nodes. To our knowledge, this is the first published report that shows the strong association of Rai stage with CXCR4 and CCR7 expression levels in B-CLL cells.

Original languageEnglish (US)
Pages (from-to)318-325
Number of pages8
JournalMayo Clinic Proceedings
Volume79
Issue number3
StatePublished - 2004

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Chemokine Receptors
B-Cell Chronic Lymphocytic Leukemia
Disease Progression
B-Lymphocytes
Lymph Nodes
Phycoerythrin
Fluorescein
Blood Cells
Color
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{299e485a72e94642bfa785f62d549a58,
title = "Expression of the Chemokine Receptors CXCR4 and CCR7 and Disease Progression in B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma",
abstract = "Objective: To assess the clinical relevance of chemokine receptor expression on the progression of B-cell chronic lymphocytic leukemia (B-CLL). Patients and Methods: Peripheral blood mononuclear cells from 45 patients with B-CLL were purified and compared with lymph node samples collected from 17 of these patients. Also compared were B cells obtained from peripheral blood samples from 5 healthy controls and B cells from reactive lymph nodes from 3 otherwise healthy persons. The patients were treated at the Mayo Clinic in Rochester, Minn, between January 15, 1991, and February 7, 2003. Mononuclear cells were stained by a 2-color (fluorescein isothiocyanate/phycoerythrin) flow cytometric assay using antibodies to the chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CCR2, CCR4, CCR5, CCR6, and CCR7) and also to CD19. Results: Of the 45 patients in this study, 20 had Rai stage 0 disease, 12 had stage I disease, 3 had stage II disease, 2 had stage III disease, and 8 had stage IV disease. The mean fluorescent intensity (MFI) of the chemokine receptor expression on B-CLL cells was compared with normal controls and was not significantly different, except for an increase in the median expression of CXCR3 (P=.003) and CCR7 (P=.001) on B-CLL cells. We also found a significant increase in the expression of CXCR4 and CCR7 in B-CLL cells from patients with stage IV compared with stage 0 disease (P=.001 and P=.02, respectively). Furthermore, circulating B-CLL cells showed significantly higher expression of CXCR4 and CCR7 when compared with B lymphocytes in lymph nodes (P=.003 and P<.001, respectively). Conclusion: The expression of CXCR4 and CCR7 on B-CLL cells correlates with Rai stage. Also, these chemokine receptors may be down-regulated once malignant B cells enter the lymph nodes. To our knowledge, this is the first published report that shows the strong association of Rai stage with CXCR4 and CCR7 expression levels in B-CLL cells.",
author = "Ghobrial, {Irene M.} and Bone, {Nancy D.} and Stenson, {Mary J.} and Novak, {Anne J} and Hedin, {Karen Elaine} and Kay, {Neil Elliot} and Ansell, {Stephen Maxted}",
year = "2004",
language = "English (US)",
volume = "79",
pages = "318--325",
journal = "Mayo Clinic Proceedings",
issn = "0025-6196",
publisher = "Elsevier Science",
number = "3",

}

TY - JOUR

T1 - Expression of the Chemokine Receptors CXCR4 and CCR7 and Disease Progression in B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

AU - Ghobrial, Irene M.

AU - Bone, Nancy D.

AU - Stenson, Mary J.

AU - Novak, Anne J

AU - Hedin, Karen Elaine

AU - Kay, Neil Elliot

AU - Ansell, Stephen Maxted

PY - 2004

Y1 - 2004

N2 - Objective: To assess the clinical relevance of chemokine receptor expression on the progression of B-cell chronic lymphocytic leukemia (B-CLL). Patients and Methods: Peripheral blood mononuclear cells from 45 patients with B-CLL were purified and compared with lymph node samples collected from 17 of these patients. Also compared were B cells obtained from peripheral blood samples from 5 healthy controls and B cells from reactive lymph nodes from 3 otherwise healthy persons. The patients were treated at the Mayo Clinic in Rochester, Minn, between January 15, 1991, and February 7, 2003. Mononuclear cells were stained by a 2-color (fluorescein isothiocyanate/phycoerythrin) flow cytometric assay using antibodies to the chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CCR2, CCR4, CCR5, CCR6, and CCR7) and also to CD19. Results: Of the 45 patients in this study, 20 had Rai stage 0 disease, 12 had stage I disease, 3 had stage II disease, 2 had stage III disease, and 8 had stage IV disease. The mean fluorescent intensity (MFI) of the chemokine receptor expression on B-CLL cells was compared with normal controls and was not significantly different, except for an increase in the median expression of CXCR3 (P=.003) and CCR7 (P=.001) on B-CLL cells. We also found a significant increase in the expression of CXCR4 and CCR7 in B-CLL cells from patients with stage IV compared with stage 0 disease (P=.001 and P=.02, respectively). Furthermore, circulating B-CLL cells showed significantly higher expression of CXCR4 and CCR7 when compared with B lymphocytes in lymph nodes (P=.003 and P<.001, respectively). Conclusion: The expression of CXCR4 and CCR7 on B-CLL cells correlates with Rai stage. Also, these chemokine receptors may be down-regulated once malignant B cells enter the lymph nodes. To our knowledge, this is the first published report that shows the strong association of Rai stage with CXCR4 and CCR7 expression levels in B-CLL cells.

AB - Objective: To assess the clinical relevance of chemokine receptor expression on the progression of B-cell chronic lymphocytic leukemia (B-CLL). Patients and Methods: Peripheral blood mononuclear cells from 45 patients with B-CLL were purified and compared with lymph node samples collected from 17 of these patients. Also compared were B cells obtained from peripheral blood samples from 5 healthy controls and B cells from reactive lymph nodes from 3 otherwise healthy persons. The patients were treated at the Mayo Clinic in Rochester, Minn, between January 15, 1991, and February 7, 2003. Mononuclear cells were stained by a 2-color (fluorescein isothiocyanate/phycoerythrin) flow cytometric assay using antibodies to the chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CCR2, CCR4, CCR5, CCR6, and CCR7) and also to CD19. Results: Of the 45 patients in this study, 20 had Rai stage 0 disease, 12 had stage I disease, 3 had stage II disease, 2 had stage III disease, and 8 had stage IV disease. The mean fluorescent intensity (MFI) of the chemokine receptor expression on B-CLL cells was compared with normal controls and was not significantly different, except for an increase in the median expression of CXCR3 (P=.003) and CCR7 (P=.001) on B-CLL cells. We also found a significant increase in the expression of CXCR4 and CCR7 in B-CLL cells from patients with stage IV compared with stage 0 disease (P=.001 and P=.02, respectively). Furthermore, circulating B-CLL cells showed significantly higher expression of CXCR4 and CCR7 when compared with B lymphocytes in lymph nodes (P=.003 and P<.001, respectively). Conclusion: The expression of CXCR4 and CCR7 on B-CLL cells correlates with Rai stage. Also, these chemokine receptors may be down-regulated once malignant B cells enter the lymph nodes. To our knowledge, this is the first published report that shows the strong association of Rai stage with CXCR4 and CCR7 expression levels in B-CLL cells.

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