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Zap-70 Identifiable with Flow Cytometry

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Prognostic Marker of Chronic Lymphocytic Leukaemia Survival

Identifiable with Flow Cytometry Assay

Lancet

01/09/2004

By Joene Hendry

In patients with chronic lymphocytic leukaemia (CLL), flow cytometry

is able to measure for ZAP-70, a tyrosine kinase protein identified

as a prognostic marker of CLL survival that is apparently equivalent

to the more difficultly identified IgVH gene mutational status.

" We have profiled gene expression in purified lymphocytes from 107

patients with CLL and shown high concordance between ZAP-70 mRNA

expression and IgVH gene mutational status, " writes G. Oscier,

FRCPath, Royal Bournemouth Hospital, United Kingdom, and colleagues,

adding " the markers were similar in their ability to identify a

subgroup of patients with short treatment-free survival. "

The investigators identified high concordance between ZAP-70 protein

expression and IgVH gene mutations in a group of 167 patients with

CLL, 61% male and a median age at diagnosis of 67 years- 65% had

mutated IgVH genes and were ZAP-70 negative while 28% had unmutated

IgVH genes and were ZAP-70 positive. Findings from the remaining

patients were discordant.

The investigators also found that expression of MRNA showed 97%

concordance with ZAP-70 protein.

In the ZAP-70 negative patients, median survival was 24.4 years while

those who were ZAP-70 positive had a median survival of 9.3 years.

" Our findings show, " the authors note, " a close correlation between

expression of ZAP-70 mRNA and protein, and between ZAP-70 protein

expression and IgVH gene mutational status. " " Clearly much more work

on ZAP-70-10 expression in CLL is needed, " they add, " but our study

represents the successful translation of cDNA microarray findings to

a flow cytometry assay that can be widely used and is of reliable

prognostic value. "

Lancet 2004;363:105-11.

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