High frequency of adhesion defects in B-lineage acute lymphoblastic leukemia

T B Geijtenbeek, Y van Kooyk, S J van Vliet, M H Renes, R A Raymakers, C G Figdor

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Aberrant proliferation, differentiation, and/or migration of progenitors observed in various hematological malignancies may be caused by defects in expression and/or function of integrins. In this study, we have developed a new fluorescent beads adhesion assay that facilitates flow cytometric investigation of lymphocyte function-associated antigen 1 (LFA-1)- and very late activation antigen-4 (VLA-4)-mediated functional adhesion in B-lineage acute lymphoblastic leukemia (ALL) of both the CD10(-) and CD10(+) (leukemic) cell population within one blood or bone marrow sample. Surprisingly, of the 20 B-lineage ALL patients investigated, 17 contained a leukemic cell population with LFA-1- and/or VLA-4-mediated adhesion defects. Five patients contained CD10(+) cells that did not exhibit any LFA-1-mediated adhesion due to the lack of LFA-1 surface expression. The CD10(+) cells from 10 ALL patients expressed LFA-1 that could not be activated by the phorbol ester phorbol 12-myristate 13-acetate (PMA), whereas the CD10(-) cells expressed a functional LFA-1. Seven patients contained CD10(+) cells that expressed a PMA-unresponsive form of VLA-4. The PMA unresponsiveness of the integrins LFA-1 and VLA-4 expressed by the CD10(+) cells may be due to mutations in the integrins itself, in protein kinases, or in other intracellular molecules involved in integrin adhesion. These data clearly demonstrate the importance of investigating integrin function in addition to integrin surface expression. The strikingly high frequency (85%) of adhesion defects in ALL could suggest a causal relationship between integrin-mediated adhesion and B-lineage ALL.

Original languageEnglish
Pages (from-to)754-64
Number of pages11
JournalBlood
Volume94
Issue number2
Publication statusPublished - 15 Jul 1999

Cite this

Geijtenbeek, T. B., van Kooyk, Y., van Vliet, S. J., Renes, M. H., Raymakers, R. A., & Figdor, C. G. (1999). High frequency of adhesion defects in B-lineage acute lymphoblastic leukemia. Blood, 94(2), 754-64.
Geijtenbeek, T B ; van Kooyk, Y ; van Vliet, S J ; Renes, M H ; Raymakers, R A ; Figdor, C G. / High frequency of adhesion defects in B-lineage acute lymphoblastic leukemia. In: Blood. 1999 ; Vol. 94, No. 2. pp. 754-64.
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abstract = "Aberrant proliferation, differentiation, and/or migration of progenitors observed in various hematological malignancies may be caused by defects in expression and/or function of integrins. In this study, we have developed a new fluorescent beads adhesion assay that facilitates flow cytometric investigation of lymphocyte function-associated antigen 1 (LFA-1)- and very late activation antigen-4 (VLA-4)-mediated functional adhesion in B-lineage acute lymphoblastic leukemia (ALL) of both the CD10(-) and CD10(+) (leukemic) cell population within one blood or bone marrow sample. Surprisingly, of the 20 B-lineage ALL patients investigated, 17 contained a leukemic cell population with LFA-1- and/or VLA-4-mediated adhesion defects. Five patients contained CD10(+) cells that did not exhibit any LFA-1-mediated adhesion due to the lack of LFA-1 surface expression. The CD10(+) cells from 10 ALL patients expressed LFA-1 that could not be activated by the phorbol ester phorbol 12-myristate 13-acetate (PMA), whereas the CD10(-) cells expressed a functional LFA-1. Seven patients contained CD10(+) cells that expressed a PMA-unresponsive form of VLA-4. The PMA unresponsiveness of the integrins LFA-1 and VLA-4 expressed by the CD10(+) cells may be due to mutations in the integrins itself, in protein kinases, or in other intracellular molecules involved in integrin adhesion. These data clearly demonstrate the importance of investigating integrin function in addition to integrin surface expression. The strikingly high frequency (85{\%}) of adhesion defects in ALL could suggest a causal relationship between integrin-mediated adhesion and B-lineage ALL.",
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Geijtenbeek, TB, van Kooyk, Y, van Vliet, SJ, Renes, MH, Raymakers, RA & Figdor, CG 1999, 'High frequency of adhesion defects in B-lineage acute lymphoblastic leukemia' Blood, vol. 94, no. 2, pp. 754-64.

High frequency of adhesion defects in B-lineage acute lymphoblastic leukemia. / Geijtenbeek, T B; van Kooyk, Y; van Vliet, S J; Renes, M H; Raymakers, R A; Figdor, C G.

In: Blood, Vol. 94, No. 2, 15.07.1999, p. 754-64.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - High frequency of adhesion defects in B-lineage acute lymphoblastic leukemia

AU - Geijtenbeek, T B

AU - van Kooyk, Y

AU - van Vliet, S J

AU - Renes, M H

AU - Raymakers, R A

AU - Figdor, C G

PY - 1999/7/15

Y1 - 1999/7/15

N2 - Aberrant proliferation, differentiation, and/or migration of progenitors observed in various hematological malignancies may be caused by defects in expression and/or function of integrins. In this study, we have developed a new fluorescent beads adhesion assay that facilitates flow cytometric investigation of lymphocyte function-associated antigen 1 (LFA-1)- and very late activation antigen-4 (VLA-4)-mediated functional adhesion in B-lineage acute lymphoblastic leukemia (ALL) of both the CD10(-) and CD10(+) (leukemic) cell population within one blood or bone marrow sample. Surprisingly, of the 20 B-lineage ALL patients investigated, 17 contained a leukemic cell population with LFA-1- and/or VLA-4-mediated adhesion defects. Five patients contained CD10(+) cells that did not exhibit any LFA-1-mediated adhesion due to the lack of LFA-1 surface expression. The CD10(+) cells from 10 ALL patients expressed LFA-1 that could not be activated by the phorbol ester phorbol 12-myristate 13-acetate (PMA), whereas the CD10(-) cells expressed a functional LFA-1. Seven patients contained CD10(+) cells that expressed a PMA-unresponsive form of VLA-4. The PMA unresponsiveness of the integrins LFA-1 and VLA-4 expressed by the CD10(+) cells may be due to mutations in the integrins itself, in protein kinases, or in other intracellular molecules involved in integrin adhesion. These data clearly demonstrate the importance of investigating integrin function in addition to integrin surface expression. The strikingly high frequency (85%) of adhesion defects in ALL could suggest a causal relationship between integrin-mediated adhesion and B-lineage ALL.

AB - Aberrant proliferation, differentiation, and/or migration of progenitors observed in various hematological malignancies may be caused by defects in expression and/or function of integrins. In this study, we have developed a new fluorescent beads adhesion assay that facilitates flow cytometric investigation of lymphocyte function-associated antigen 1 (LFA-1)- and very late activation antigen-4 (VLA-4)-mediated functional adhesion in B-lineage acute lymphoblastic leukemia (ALL) of both the CD10(-) and CD10(+) (leukemic) cell population within one blood or bone marrow sample. Surprisingly, of the 20 B-lineage ALL patients investigated, 17 contained a leukemic cell population with LFA-1- and/or VLA-4-mediated adhesion defects. Five patients contained CD10(+) cells that did not exhibit any LFA-1-mediated adhesion due to the lack of LFA-1 surface expression. The CD10(+) cells from 10 ALL patients expressed LFA-1 that could not be activated by the phorbol ester phorbol 12-myristate 13-acetate (PMA), whereas the CD10(-) cells expressed a functional LFA-1. Seven patients contained CD10(+) cells that expressed a PMA-unresponsive form of VLA-4. The PMA unresponsiveness of the integrins LFA-1 and VLA-4 expressed by the CD10(+) cells may be due to mutations in the integrins itself, in protein kinases, or in other intracellular molecules involved in integrin adhesion. These data clearly demonstrate the importance of investigating integrin function in addition to integrin surface expression. The strikingly high frequency (85%) of adhesion defects in ALL could suggest a causal relationship between integrin-mediated adhesion and B-lineage ALL.

KW - Adolescent

KW - Adult

KW - B-Lymphocytes/chemistry

KW - Bone Marrow/pathology

KW - Burkitt Lymphoma/blood

KW - Cell Adhesion

KW - Flow Cytometry

KW - Humans

KW - Integrin alpha4beta1

KW - Integrins/analysis

KW - Intercellular Adhesion Molecule-1/metabolism

KW - Lymphocyte Function-Associated Antigen-1/analysis

KW - Microspheres

KW - Middle Aged

KW - Neoplasm Proteins/analysis

KW - Neoplastic Stem Cells/chemistry

KW - Neprilysin/analysis

KW - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/blood

KW - Receptors, Lymphocyte Homing/analysis

KW - Tetradecanoylphorbol Acetate/pharmacology

KW - Vascular Cell Adhesion Molecule-1/metabolism

M3 - Article

VL - 94

SP - 754

EP - 764

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -

Geijtenbeek TB, van Kooyk Y, van Vliet SJ, Renes MH, Raymakers RA, Figdor CG. High frequency of adhesion defects in B-lineage acute lymphoblastic leukemia. Blood. 1999 Jul 15;94(2):754-64.