Although it is premature to recommend therapy based on these risk factors, patients with ZAP-70-positive CLL cells should be monitored closely for disease progression as they have a median time from diagnosis to requiring initial therapy by standard criteria of approximately 3 years.
These data point to the need for a more extensive study to evaluate the significance of Zap-70 and CD38 expression as indicators of IgVH mutation status and prognosis of CLL patients.
Some new prognostic factors, such as immunoglobulin variable heavy chain (IgVH) mutational status, zeta-associated protein (ZAP-70) and CD38 expression in leukemic cells were introduced to identify attenuated versus progressive types of CLL bearing the potential to facilitate risk-adapted treatment strategies.
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.
Additionally, ZAP-70 expression in CLL cells confers markedly heightened sensitivity to 17-AAG or 17-DMAG, suggesting that these or other Hsp90 inhibitors could be valuable therapeutically in patients with aggressive CLL.
In particular, ZAP-70 is especially attractive because its aberrant expression in tumour cells from the more aggressive forms of CLL requires the chaperoning action of activated heat-shock protein 90, which may be specifically inhibited.
These data show the characterization and generation of a novel murine leukemia model with many similarities to human ZAP-70+ B cell chronic lymphocytic leukemia.
In 7 patients, ZAP-70 expression and IgVH mutation status were discordant: 4 Ig-mutated CLLs had high ZAP-70 expression and 3 Ig-unmutated CLLs had low ZAP-70 expression.