ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia.

N Engl J Med 2003 May;348(18):1764-75

Department of Hematology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.

Background: The 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.

Methods: The 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.

Results: ZAP-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.

Conclusions: Among patients with CLL, expression of ZAP-70, as detected by flow-cytometric analysis, correlated with IgVH mutational status, disease progression, and survival.

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Source
http://www.nejm.org/doi/abs/10.1056/NEJMoa023143
Publisher Site
http://dx.doi.org/10.1056/NEJMoa023143DOI Listing
May 2003
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