Adhesion of acute myeloid leukemia (AML) blasts in the bone marrow microenviron- ment confers protection from chemo- therapy-induced apoptosis. One mecha- nism for retention of blasts within the bone marrow is adhesion via very late antigen-4 (VLA-4), the a4β1 integrin heterodimer that binds to its main ligands, fibronectin. and vascular cell adhesion molecule-1 (VCAM- 1). To examine the relationship of functional expression of VLA-4 to prognosis in AML, we studied marrow samples from 175 adult AML patients who underwent induction che- motherapy with anthracycline and cytara- bine on Southwest Oncology Group trials. The studies included flow cytometry and functional in vitro assays for ligand binding and maximal β1 activation. VLA-4 expres- sion varied widely, with mean expression 60.6% for a4, and was not significantly asso- ciated with response to chemotherapy, relapse-free, or overall survival (OS). How- ever, increased binding of soluble VCAM-1 via VLA-4 was significantly associated with longer OS, corrected for age (P = .033). Esti- mated 5-year OS was 31% (95% confidence interval, 14%-48%) in 30 patients with soluble VCAM-1 binding greater than or equal to 40%, compared with 10% (confidence inter- val, 3%-17%) in 72 patients with lower bind- ing. Adhesion and migratory properties of AML blasts thus appear to influence chemo- sensitivity and therefore may be therapeutic targets.
ASJC Scopus subject areas
- Cell Biology