Corcoran, M. M., Parker, A. E., Orchard, J. A., Davis, Z. A., Wirtz, M., Schmitz, O. J. and Oscier, D. G., 2005. ZAP-70 methylation status is associated with ZAP-70 expression status in chronic lymphocytic leukemia. Haematologica, 90 (8), pp. 10178-1088.
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Official URL: http://www.haematologica.org/cgi/content/abstract/...
ZAP-70 expression is a recognized prognostic marker in chronic lymphocytic leukemia (CLL). The aim of this study was to analyze whether the methylation status of the ZAP-70 gene is associated with expression of the ZAP-70 protein. DESIGN AND METHODS: Patients with CLL (n=87), acute lymphoblastic leukemia (n=13), mantle cell leukemia (n=13) and splenic marginal zone lymphoma (n=14) of known immunoglobulin gene mutation (IgVH) status were studied. The methylation status of the 5' region of ZAP-70 was analyzed by combined bisulphite restriction analysis (COBRA), southern blotting and bisulphite sequencing in 10 CLL patients and in normal T/NK and B cells. Further COBRA of a single CpG site located 334bp downstream of the ZAP-70 transcription start site (C-334) was then performed on all patients. RESULTS: ZAP-70 expression status in CLL and normal peripheral blood lymphocytes is associated with the methylation status of the intron1-exon2 boundary region of ZAP-70 and methylation status of C-334 determined by COBRA is representative of methylation in this region. Of 87 CLL patients, 51/53 ZAP-70 negative patients had methylation at C-334 and 30/32 ZAP-70 positive patients did not have methylation (p<0.0001); a similar association was seen in all other diseases. Median survivals of methylated and unmethylated CLL patients were 211 and 85 months, respectively (p<0.0001). INTERPRETATION AND CONCLUSIONS: Measuring ZAP-70 methylation status at C-334 is a simple and reproducible method for predicting prognosis in CLL, which is closely associated with ZAP-70 expression and IgVH gene mutational status. Methylation of a highly conserved intronic region of ZAP-70 may be responsible for regulation of expression in normal and neoplastic cells.
|Subjects:||Technology > Medicine and Health|
|Group:||School of Health and Social Care > Centre for Postgraduate Medical Research and Education|
|Deposited By:||INVALID USER|
|Deposited On:||02 Nov 2008 16:13|
|Last Modified:||07 Mar 2013 14:51|
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