ZAP-70 immunoreactivity is a prognostic marker of disease progression in chronic lymphocytic leukemia

Claudia Vener, Umberto Gianelli, Agostino Cortelezzi, Nicola Stefano Fracchiolla, Franco Somalvico, Federica Savi, Maria Cristina Pasquini, Silvano Bosari, Giorgio Lambertenghi Deliliers

Research output: Contribution to journalArticlepeer-review


The expression of zeta-associated protein 70 (ZAP-70) in chronic lymphocytic leukemia (CLL) seems to correlate with the mutational status of the immunoglobulin heavy-chain variable-region genes, clinical course and patient prognosis. The aim was to determine the prognostic significance of the immunohistochemical expression of ZAP-70 protein in CLL by means of the long-term follow-up of 108 patients. This study identified 3 patterns of ZAP-70 immunoreactivity: negative (58 patients, 54%), weakly positive (20 patients, 18%) and strongly positive (30 patients, 28%). Overall, ZAP-70 immunoreactivity correlated with an abnormal karyotype (p = 0.017), a lymphocyte doubling time (LDT) of <6 months (p = 0.001) and <12 months (p = 0.01), Rai II - IV and Binet B-C stage (p = 0.013), the clinical need for chemotherapy (p <0.001) and the need for more than 1 chemotherapy line (p <0.001). Kaplan-Meier analysis demonstrated that ZAP-70 immunoreactivity closely correlated with a shorter LDT (p <0.0001) and time from diagnosis to initial therapy (p = 0.0001). The same significance was retained when the patients were stratified into the ZAP-70 immunoreactivity groups (p <0.0001). This study shows that ZAP- immunoreactivity can be a reliable prognostic marker in CLL and proposes a system for evaluating the results. The observations support the inclusion of the immunohistochemical expression of ZAP-70 in clinical trials involving CLL patients.

Original languageEnglish
Pages (from-to)245-251
Number of pages7
JournalLeukemia and Lymphoma
Issue number2
Publication statusPublished - Feb 2006


  • Chronic lymphocytic leukemia
  • Immunohistochemistry
  • ZAP-70 protein

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology


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