Serum CD26 (Dipeptidyl Peptidase IV, DPP IV) compared with Immunoglobulin Heavy-Chain Mutation Status, ZAP-70 and CD38 as a Predictor of Time to First Treatment in Early B-CELL Chronic Lymphocytic Leukemia

Abstract

We analyzed the correlation between well-established biological parameters of prognostic relevance in B-chronic lymphocytic leukemia [CLL] (i.e, mutational status of the immunoglobulin heavy chain variable region [IgVH], ZAP-70- and CD38-expression) and serum levels of CD26 (dipeptidyl peptidase IV, DPP IV) by evaluating the impact of these variables on the time to first treatment [TFT] in a series of 69 previously untreated Binet stage A B-CLL patients. By using a commercial ELISA (Human DPPIV/CD26 Quantikine R D Systems, USA) we found that circulating levels of CD26 did not reflect Rai sub-stages (P=0.52), β2-microglobulin (P=0.68), LDH (P=0.06), mutational status of IgVH (P=0.28), ZAP-70 (P=0.52) and CD38 (P=0.48). We used an optimal cut-point search to determine how to best split soluble CD26 data. Maximally selected logrank statistics plots identified a CD26 serum concentration of 371 ng/mL as the best cut-off. Accordingly, patients who had CD26 levels higher than 371 ng/mL experienced a shorter TFT (median 40 months) in comparison to patients whose CD26 levels were lower than 371 ng/mL (median 120 months; P=0.003). The univariate Cox proportional hazard model identified higher serum concentration of CD26 and absence of mutation in IgVH as predictor of shorter TFT. Again in multivariate analysis all these parameters maintained their discriminating power: mutational status of IgVH (HR= 0.23; CI 95% 0.10−0.51, P<0.0001), soluble CD26 (HR= 0.38; CI 95% 0.17−0.85, P=0.02). The effects of CD26 on TFT were masked by mutational status of IgVH in patients with unmutated IgVH. In contrast, serum levels of CD26 and mutational status of IgVH had a joint effect on TFT in patients with mutated IgVH which translates into a segregation of patients with mutated IgVH in two sub-groups with different TFT according to CD26 levels (HR= 0.18; CI 95% 0.05−0.60, P=0.005). Our results indicate that in early B-cell CLL biological profile including among other parameters soluble CD26 may provide a useful insight into the complex interrelationship of prognostic variables. Furthermore, CD26 along with mutational status of IgVH can be adequately used to predict clinical behaviour of patients with low biological risk.