Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells.
Adhesion of hematopoietic progenitor cells to marrow-derived adherent cells has been noted for erythroid, myeloid, and lymphoid precursors. In this report, we have characterized very late antigen (VLA) integrin expression on normal CD34+ marrow progenitors, on leukemic cell lines, and on blasts from patients with acute myelogenous or monocytic leukemias. CD34+ progenitor cells expressed the integrin beta 1 chain (CD29), VLA-4 alpha (CD49d), and VLA-5 alpha (CD49e). The myeloid lines KG1 and KG1a also expressed CD49d and CD49e as did the Mo7e megakaryoblastic line. CD29, CD18, and CD11a were also present on each of these cell lines. Only the Mo7e line expressed the cytoadhesins GPIIbIIIa or GPIb. Binding of KG1a to marrow stroma was partially inhibited by antibodies to CD49d and its ligand, vascular cell adhesion molecule (VCAM-1). The majority of leukemic blasts studied expressed CD49d and CD49e as well. Blasts from patients with acute myelomonocytic leukemia consistently bound to stroma at levels greater than 20%, and adhesion to stroma could in some cases be partly inhibited by anti-CD49d. No role for glycosylphosphatidyl-inositol (GPI)-linked structures was demonstrated in these binding assays because the adhesion of leukemic blasts to stroma was not diminished after treatment with phosphatidylinositol-specific phospholipase C (PI-PLC). These studies indicate that CD34+ myeloid progenitors, myeloid leukemic cell lines, and leukemic blasts possess a similar array of VLA integrins. Their functional importance individually or in combination with other mediators of attachment in adhesion, transendothelial migration, and differentiation has yet to be fully elucidated.
Liesveld
J L
JL
Hematology Unit, University of Rochester Medical Center, NY 14642.
Winslow
J M
JM
Frediani
K E
KE
Ryan
D H
DH
Abboud
C N
CN
D000906:Antibodies; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D016023:Integrins / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology; D007938:Leukemia / Q000473:pathology*; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015703:Antigens, CD; D018952:Antigens, CD34; D016023:Integrins; D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor