Comparison of ZAP-70/Syk mRNA levels with immunoglobulin heavy-chain gene mutation status and disease progression in chronic lymphocytic leukemia
Department of Hematology, Catholic University Hospial A. Gemelli, Rome, Italy. laurenti@rm.unicatt.it BACKGROUND AND OBJECTIVES: The protein tyrosine kinase ZAP-70 has recently emerged as a major prognostic indicator in chronic lymphocytic leukemia (CLL). ZAP-70 is structurally and functionally homo...
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Veröffentlicht in: | Haematologica (Roma) 2005-11, Vol.90 (11), p.1533-1540 |
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Sprache: | eng |
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Zusammenfassung: | Department of Hematology, Catholic University Hospial A. Gemelli, Rome, Italy. laurenti@rm.unicatt.it
BACKGROUND AND OBJECTIVES: The protein tyrosine kinase ZAP-70 has recently emerged as a major prognostic indicator in chronic lymphocytic leukemia (CLL). ZAP-70 is structurally and functionally homologous to Syk, a key mediator of B-cell receptor signaling. We therefore evaluated ZAP-70 expression in CLL B cells using Syk as an intracellular standard. DESIGN AND METHODS: The relative amounts of ZAP-70 and Syk were determined in purified B cells from 92 CLL patients using a novel reverse transcriptase/polymerase chain reaction (RT-PCR) procedure that co-amplifies both transcripts with equal efficiency. The ZAP-70/Syk mRNA ratio was correlated with VH gene mutation status, median treatment-free survival and FACS analysis of ZAP-70 expression. RESULTS: ZAP-70 was expressed in the majority of cases with unmutated VH genes (88%), but also at lower levels in a substantial fraction of cases with mutated VH genes (44%). High levels of ZAP-70, defined as ZAP-70/Syk mRNA ratios above 0.25, were observed mainly in cases with unmutated VH genes and correlated with short treatment-free survival. In contrast, no difference was observed in the median treatment-free survival between patients with low ZAP-70/Syk ratios (0.05-0.25) and patients with no or negligible ZAP-70 expression (ZAP-70/Syk |
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ISSN: | 0390-6078 1592-8721 |