Interferon-alpha restores beta1-integrin-dependent, collagen-mediated platelet aggregation in a patient with chronic myelogenous leukemia.
Although interferon-alpha (IFN-alpha) induces hematologic remissions in 70% to 80% of patients with chronic myelogenous leukemia (CML) and complete or near-complete cytogenetic remissions in 10% to 20% of patients, the exact mechanisms underlying these clinical results remain unclear. We have hypothesized that IFN-alpha acts at least in part through restoration of beta1-integrin function on malignant hematopoietic progenitors that can promote adhesion of malignant progenitors to the marrow microenvironment. This may then restore microenvironmental inhibition of progenitor proliferation and induce tumor dormancy. We demonstrate that IFN-alpha administration to a patient suffering from a clinically severe bleeding diathesis reversed the defective collagen-mediated aggregation of platelets expressing normal numbers of functionally inactive collagen receptors. This is the first in vivo demonstration that IFN-alpha can up-regulate the function of adhesion receptors in CML and supports the premise that IFN-alpha induces remissions by restoring normal integrin-mediated interactions between progenitors and microenvironmental components.
Verfaillie
C M
CM
Department of Medicine, University of Minnesota Medical School, Minneapolis, USA.
Bhatia
R
R
Browne
P
P
Key
N S
NS
D003094:Collagen / Q000502:physiology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D016130:Immunophenotyping; D019012:Integrin beta1 / Q000502:physiology*; D016898:Interferon-alpha / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D010974:Platelet Aggregation / Q000502:physiology*
D019012:Integrin beta1; D016898:Interferon-alpha; D003094:Collagen; D006918:Hydroxyurea