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- Title
Correlation of ZAP-70 expression in B cell leukemias to the ex vivo response to a combination of fludarabine/genistein.
- Authors
Mansour, Amal; Chang, Victor T.; Srinivas, Shanti; Harrison, Jonathan; Raveche, Elizabeth
- 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.
- Subjects
B cells; LEUKEMIA; FLUDARABINE; PURINES; MESSENGER RNA; APOPTOSIS
- Publication
Cancer Immunology, Immunotherapy, 2007, Vol 56, Issue 4, p501
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-006-0207-x