Very late antigen-4 function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemia

Pamela S. Becker, Kenneth J. Kopecky, Adrianne N. Wilks, Sylvia Chien, John M. Harlan, Cheryl L. Willman, Stephen H. Petersdorf, Derek L. Stirewalt, Thalia Papayannopoulou, Frederick R. Appelbaum

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)866-874
Number of pages9
JournalBlood
Volume113
Issue number4
DOIs
StatePublished - Jan 22 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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