Comparison of Genomic Aberrations and Expression of ZAP-70 and CD38.

Expression of CD38 and /or ZAP 70 and chromosome abnormalities such as deletions of 11q23 and 17p13 have been previously identified by several groups as predictors of disease progression and decrease overall survival in Chronic Lymphocytic Leukemia (CLL). Moreover, few are described about the relationship between ZAP70/CD38 status and their genomic aberrations associated.

We analysed 86 patients (median age: 70 yrs; female/male: 28/58) diagnosed of CLL between 1980 and 2005. Cytoplasmic ZAP-70 expression and cell surface expression of CD38, was determined by flow cytometry in CD19+ CD5+ B-CLL cells. Trisomy 12 and deletions in 13q14, 11q22–23 and 17p13, were detected by the interphase cytogenetic fluorescence in situ hybridization (FISH). Biological study in patients diagnosed before 2001 was done on cryopreserved blood cells.

Concordant expression of ZAP-70 and CD38 was seen in 66 of 86 patients (76%). Fifty-one patients were ZAP-70- and CD38-, and 15 patients were ZAP-70+ and CD38+. Discordant ZAP70/CD38 status was present in 20 patients. Cytogenetic study identified chromosome aberrations in 85% of patients. Deletions in band 13q14 (43%), followed by trisomy 12 (21%), deletions in 11q22–23 (11%) and in 17p13 (10%) were the most frequent abnormalities. Normal karyotype was presented in 28% of patients and complex karyotype in 11%.

In the concordant ZAP70-CD38- cases and ZAP70+ CD38+, 13q14 aberration (47, 9%) and normal karyotype (42%) respectively, were more frequent than in the other groups but in our study this differences were not statistically significant. Moreover deletion in 11q22–23 (25%) was seen statistically significant, p = 0, 05, in patients with concordant expression of ZAP70+ and CD38+. Patients with discordant status in the expression of ZAP70 and CD38, were statistically associated with trisomy 12 (38%) p = 0,002.

In conclusion, in our study we find that expression in ZAP70 and CD38 is associated with a different genomic aberration. Deletion in 13q14 appears more frequent in patients with concordant ZAP70- and CD38- expression. Trisomy 12 is associated with discordant status expression. Finally, the worse prognostic group ZAP70+ and CD38+ is associated with a normal karyotype or deletions in 11q22–23.