ZAP-70 Expression Can be Assessed by the ZAP-70/Syk mRNA Ratio

November 7, 2005

Haematologica. 2005 Nov;90(11):1533-40.

Comparison of ZAP-70/Syk mRNA levels with immunoglobulin heavy-chain

gene mutation status and disease progression in chronic lymphocytic

leukemia.

ti L, Petlickovski A, Rumi C, Gobessi S, Piccioni P, Tarnani M,

Puggioni P, Marietti S, Sica S, Leone G, Efremov DG.

Department of Hematology, Catholic University Medical School, Largo

A.Gemelli 8, I-00168 Rome, Italy. laurenti@....

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<0.05).

In 73 cases ZAP-70 expression was investigated by RT/PCR and FACS

analysis; concordance with VH gene mutation status was 86% and 71%,

respectively.

INTERPRETATION AND CONCLUSIONS: ZAP-70 is frequently expressed in CLL

B cells, but only high levels correlate with unmutated VH gene status

and progressive disease. Expression of ZAP-70 can be accurately

assessed by analysis of the ZAP-70/Syk mRNA ratio, thus providing an

alternative to FACS analysis.

PMID: 16266901 [PubMed - in process]

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