ZAP-70, CD38, and Chromosomal Abnormalities

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[5004] Comparison of Genomic Aberrations and Expression of ZAP-70 and

CD38. Session Type: Publication Only

Lucrecia Yañez, Angeles Cuadrado, Andres Insunza, Arancha

Bermudez, Belen Mesones, Eulogio Conde, Encarna Bureo,

Arturo Iriondo Hematologia, Hospital Universitario Marqués de

Valdecilla, Santander, Cantabria, Spain

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.