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ZAP-70 Expression as a Surrogate for Immunoglobulin-Variable-Region Mutations in Chronic Lymphocytic Leukemia

ZAP-70 Expression as a Surrogate for Immunoglobulin-Variable-Region Mutations in Chronic... BackgroundThe mutational status of immunoglobulin heavy-chain variable-region (IgVH) genes in the leukemic cells of chronic lymphocytic leukemia (CLL) is an important prognostic factor in the disease. We investigated whether the expression of ZAP-70 by CLL cells correlated with the IgVH mutational status, disease progression, and survival.MethodsThe expression of ZAP-70 was analyzed in T-cell and B-cell lines and in peripheral-blood samples from 56 patients with CLL with the use of flow cytometry, Western blotting, and immunohistochemistry. The results were correlated with the IgVH mutational status and clinical outcome.ResultsZAP-70 was detected by flow-cytometric analysis in cells of T-cell lineage and in leukemic cells from 32 of 56 patients with CLL. In all patients in whom at least 20 percent of the leukemic cells were positive for ZAP-70, IgVH was unmutated, whereas IgVH mutations were found in 21 of 24 patients in whom less than 20 percent of the leukemic cells were positive for ZAP-70 (P<0.001). Concordant results were obtained when ZAP-70 expression was assessed by immunohistochemistry or Western blotting. The level of ZAP-70 expression did not change over time (median, 37 months) in sequential samples from 30 patients with CLL. Patients with Binet stage A CLL who had at least 20 percent ZAP-70–positive leukemic cells had more rapid progression and poorer survival than those with less than 20 percent ZAP-70–positive cells.ConclusionsAmong patients with CLL, expression of ZAP-70, as detected by flow-cytometric analysis, correlated with IgVH mutational status, disease progression, and survival. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The New England Journal of Medicine The New England Journal of Medicine

ZAP-70 Expression as a Surrogate for Immunoglobulin-Variable-Region Mutations in Chronic Lymphocytic Leukemia

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References (32)

Publisher
The New England Journal of Medicine
Copyright
Copyright © 2003 Massachusetts Medical Society. All rights reserved.
ISSN
0028-4793
eISSN
1533-4406
DOI
10.1056/NEJMoa023143
pmid
12724482
Publisher site
See Article on Publisher Site

Abstract

BackgroundThe mutational status of immunoglobulin heavy-chain variable-region (IgVH) genes in the leukemic cells of chronic lymphocytic leukemia (CLL) is an important prognostic factor in the disease. We investigated whether the expression of ZAP-70 by CLL cells correlated with the IgVH mutational status, disease progression, and survival.MethodsThe expression of ZAP-70 was analyzed in T-cell and B-cell lines and in peripheral-blood samples from 56 patients with CLL with the use of flow cytometry, Western blotting, and immunohistochemistry. The results were correlated with the IgVH mutational status and clinical outcome.ResultsZAP-70 was detected by flow-cytometric analysis in cells of T-cell lineage and in leukemic cells from 32 of 56 patients with CLL. In all patients in whom at least 20 percent of the leukemic cells were positive for ZAP-70, IgVH was unmutated, whereas IgVH mutations were found in 21 of 24 patients in whom less than 20 percent of the leukemic cells were positive for ZAP-70 (P<0.001). Concordant results were obtained when ZAP-70 expression was assessed by immunohistochemistry or Western blotting. The level of ZAP-70 expression did not change over time (median, 37 months) in sequential samples from 30 patients with CLL. Patients with Binet stage A CLL who had at least 20 percent ZAP-70–positive leukemic cells had more rapid progression and poorer survival than those with less than 20 percent ZAP-70–positive cells.ConclusionsAmong patients with CLL, expression of ZAP-70, as detected by flow-cytometric analysis, correlated with IgVH mutational status, disease progression, and survival.

Journal

The New England Journal of MedicineThe New England Journal of Medicine

Published: May 1, 2003

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