CD26 Expression in Mature B-Cell Neoplasia: Its Possible Role as a New Prognostic Marker in B-CLL.

Abstract

CD26 (dipeptidyl peptidase IV, DPP IV) is a multifunctional type II cell surface glycoprotein that is widely expressed on T and natural killer cells, as well as on epithelial, endothelial and acinar cells of different tissues; its expression on B cells is very low but it is greatly upregulated following activation. We evaluated, by means of flow cytometry, the expression of CD26 in various types of B-cell lymphoid tumors: Follicular Lymphoma (Fo-Ly, 12 cases), Mantle cell Lymphoma (MCL, 12 cases) Multiple Myeloma (MM, 20 cases), Hairy cell Leukemia (HCL, 12 cases), B-cell Chronic Lymphocytic Leukemia (B-CLL, 112 cases), CD5 negative B-cell Chronic Lymphoproliferative Diseases (CD5neg-B-CLPD, 20 cases) and Diffuse Large cell Lymphoma (DLCL, 12 cases). CD26 expression was absent or low of Fo-Ly and MCL, high on MM and HCL, variable on B-CLL, CD5neg-B-CLPD and DLCL. Fluorescence intensity of positive cells was dim in B-CLL and CD5neg-B-CLPD, heterogeneous in DLCL, and bright in HCL and MM. Interestingly, in CLL patients, CD26 expression was significantly correlated with CD49d and CD38 expressions (p<0.0001); moreover Spearman's test revealed a significant correlation between CD26, CD38 or ZAP-70 expression and IgVH mutational status (p<0.0001). We also found a significant correlation between CD26 expression and the presence of FISH chromosomal abnormalities grouped on the basis of their prognostic relevance (p<0.0001). After a median follow-up of 36 months, 65/107 CLL pts were treated; taking 10% of positive cells as best cut-off, Kaplan-Meier curves showed that the time without therapy was significantly longer for CD26 negative cases compared with CD26 positive cases (P <0.0001). Moreover the concordant negativity of CD26 and CD38, or ZAP-70 and the combination of CD26 negativity with IgVH mutated status, identified subsets of CLL patients with a favourable outcome in terms of need of therapy.