alpha4beta1 integrin-mediated adhesion of CD34+ cells from patients with chronic myeloid leukaemia: influence of IL-3.
Interactions between integrins on haemopoietic progenitor cells and their stromal ligands have an important role in the control of haemopoiesis. Growth factors can modulate these interactions (so-called 'inside-out' signalling) resulting in changes in ligand binding activity. We have studied alpha4beta1 integrin-mediated adhesion to the H120 fragment of fibronectin (which contains the strongest alpha4beta1 binding site) in CD34+ cells from patients with chronic myeloid leukaemia (CML) and have determined the effect of IL-3 on the level of adhesion. Compared to normal CD34+ cells isolated from cord blood and peripheral blood progenitor harvests (mean of 61.4 +/- 14.9% of cells attached) the CML CD34+ cells showed reduced levels of adhesion (mean of 41.9 +/- 14.7%, P < 0.05). The effect of 10 ng/ml of IL-3 resulting in reduced adhesion of normal CD34+ cells at 30 min was absent in 6/7 patients with CML. Abnormalities of adhesion to fibronectin may thus be related to IL-3 pathways affected by BCR-ABL. These findings will have implications for understanding the dysregulation of growth and adhesion in CML.
Schofield
K P
KP
Department of Medical Oncology, Paterson Institute for Cancer Research, Manchester, UK.
Duerig
J
J
Rushton
G
G
Chang
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018926:Anti-Allergic Agents / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D013997:Time Factors
D018926:Anti-Allergic Agents; D018952:Antigens, CD34; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D007377:Interleukin-3; D016201:Receptors, Lymphocyte Homing