Interferon-α restores β1-integrin-dependent, collagen-mediated platelet aggregation in a patient with chronic myelogenous leukemia

Academic Article

Abstract

  • Although interferon-α (IFN-α) 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-α acts at least in part through restoration of β1-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-α 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-α can up-regulate the function of adhesion receptors in CML and supports the premise that IFN-α induces remissions by restoring normal integrin-mediated interactions between progenitors and microenvironmental components.
  • Digital Object Identifier (doi)

    Author List

  • Verfaillie CM; Bhatia R; Browne P; Key NS
  • Start Page

  • 163
  • End Page

  • 169
  • Volume

  • 131
  • Issue

  • 2