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

• Published in: Blood 1999-07, Vol.94 (2), p.754-764
• Main Authors: GEIJTENBEEK, T. B. H, VAN KOOYK, Y, VAN VLIET, S. J, RENES, M. H, RAYMAKERS, R. A. P, FIGDOR, C. G
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; B-Lymphocytes - chemistry; B-Lymphocytes - drug effects; B-Lymphocytes - pathology; Biological and medical sciences; Bone Marrow - pathology; Burkitt Lymphoma - blood; Burkitt Lymphoma - pathology; Cell Adhesion; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Integrin alpha4beta1; Integrins - analysis; Integrins - deficiency; Intercellular Adhesion Molecule-1 - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Function-Associated Antigen-1 - analysis; Medical sciences; Microspheres; Middle Aged; Neoplasm Proteins - analysis; Neoplasm Proteins - deficiency; Neoplastic Stem Cells - chemistry; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; Neprilysin - analysis; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Receptors, Lymphocyte Homing - analysis; Receptors, Lymphocyte Homing - deficiency; Tetradecanoylphorbol Acetate - pharmacology; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v94.2.754

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.