BACKGROUND: The course of chronic lymphocytic leukemia (CLL) is variable. In aggressive disease, the CLL cells usually express an unmutated immunoglobulin heavy-chain variable-region gene (IgV H) and the 70-kD zeta-associated protein (ZAP-70), whereas in indolent disease, the CLL cells usually express mutated IgV H but lack expression of ZAP-70. METHODS: We evaluated the CLL B cells from 307 patients with CLL for ZAP-70 and mutations in the rearranged IgV H gene. We then investigated the association between the results and the time from diagnosis to initial therapy. RESULTS: We found that ZAP-70 was expressed above a defined threshold level in 117 of the 164 patients with an unmutated IgV H gene (71 percent), but in only 24 of the 143 patients with a mutated IgV H gene (17 percent, P<0.001). Among the patients with ZAP-70-positive CLL cells, the median time from diagnosis to initial therapy in those who had an unmutated IgV H gene (2.8 years) was not significantly different from the median time in those who had a mutated IgV H gene (4.2 years, P=0.07). However, the median time from diagnosis to initial treatment in each of these groups was significantly shorter than the time in patients with ZAP-70-negative CLL cells who had either mutated or unmutated IgV H genes (P<0.001). The median time from diagnosis to initial therapy among patients who did not have ZAP-70 was 11.0 years in those with a mutated IgV H gene and 7.1 years in those with an unmutated IgV H gene (P<0.001). CONCLUSIONS: Although the presence of an unmutated IgV H gene is strongly associated with the expression of ZAP-70, ZAP-70 is a stronger predictor of the need for treatment in B-cell CLL.
ASJC Scopus subject areas