Cancer Immunology, Immunotherapy

, Volume 56, Issue 4, pp 501–514

Correlation of ZAP-70 expression in B cell leukemias to the ex vivo response to a combination of fludarabine/genistein

  • Amal Mansour
  • Victor T. Chang
  • Shanti Srinivas
  • Jonathan Harrison
  • Elizabeth Raveche
Original Article

Abstract

The role of ZAP-70 expression on the ex vivo response of blood cells from CLL and PLL patients to a combination of fludarabine, a purine analog, and genistein, a tyrosine kinase inhibitor was studied. Patient cells were studied for the expression of ZAP-70 mRNA and its relation to the induction of apoptosis in response to treatment with genistein 15–60 μM and/or fludarabine 3 μM. The combination of genistein and fludarabine resulted in a significantly increased induction of apoptosis relative to the fludarabine alone. The ex vivo patient cells with a high ZAP-70 expression underwent more apoptosis in response to genistein than did patient cells with a low ZAP-70 mRNA expression. In contrast, basal IL-10 mRNA expression correlated negatively with apoptosis induction in response to genistein (P < 0.01). These studies suggest that, in malignant B cells that express elevated levels of the ZAP-70 signaling molecule, genistein may inhibit the ZAP-70 tyrosine kinase activity, resulting in cell death. The ZAP-70 may serve as a target for therapy. In addition, these studies suggest that the IL-10 expression by malignant B cells may not only suppress anti-tumor T cell responses in vivo, but also promote the survival of malignant B cells despite treatment with chemotherapeutic agents.

Keywords

Genistein Chronic lymphoproliferative leukemia Fludarabine IL-10 Apoptosis ZAP-70 

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Amal Mansour
    • 1
  • Victor T. Chang
    • 1
    • 2
    • 3
  • Shanti Srinivas
    • 1
    • 2
    • 3
  • Jonathan Harrison
    • 1
  • Elizabeth Raveche
    • 1
    • 4
  1. 1.Department of Pathology, New Jersey Medical SchoolUMDNJNewarkUSA
  2. 2.Section of Hematology/Oncology VA New Jersey Health Care SystemEast OrangeUSA
  3. 3.Department of Medicine, New Jersey Medical SchoolUMDNJNewarkUSA
  4. 4.Department of Pathology and Laboratory Medicine, New Jersey Medical School, UMDNJNewarkUSA

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