- N Engl J
Med. 2003 May 1;348(18):1764-75.
Comment in: N Engl J Med. 2003 Jul 31;349(5):506-7; author reply
506-7. N Engl J Med. 2003 May
1;348(18):1797-9.
ZAP-70 expression as a surrogate for
immunoglobulin-variable-region mutations in chronic lymphocytic
leukemia.
Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman
M, Marce S, Lopez-Guillermo A, Campo E, Montserrat E.
Department of Hematology, Institut d'Investigacions Biomediques
August Pi i Sunyer, Hospital Clinic, 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. Copyright 2003 Massachusetts Medical
Society
PMID: 12724482 [PubMed - indexed for MEDLINE]
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