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 widely expressed by T and natural killer (NK) cells, epithelial and endothelial cells of different tissues, and it is strongly upregulated in activated B-cells; moreover it plays a regulatory role in the neoplastic transformation and progression of various types of tumours. CD26 expression was evaluated by means of flow cytometry in various peripheral B-cell lymphoid tumours: 12 follicular and 12 mantle cell lymphomas, 20 multiple myelomas (MMs), 12 hairy cell leukaemias (HCLs), 112 chronic lymphocytic leukaemias (CLLs), 20 CD5(negative) B-cell chronic lymphoproliferative diseases (CD5(neg) B-CLPDs) and 12 diffuse large cell lymphomas (DLCLs). CD26 expression was absent or barely detectable in follicular and mantle cell lymphomas, high in MMs and HCLs, and variable in CLLs, in CD5(neg) B-CLPDs and in DLCLs. CD26 significantly correlated with CD49d and CD38 expressions (p < 0.0001) in B-CLLs, and there was a significant correlation between CD26 and ZAP-70 expressions or IgVH mutational status (p < 0.0001). After a median follow-up of 36 months, 65 B-CLL patients were treated; taking 10% as the best CD26 cut-off value, Kaplan-Meier curves revealed a significantly shorter time to treatment in the CD26-positive cases (p < 0.0001). Overall, our data indicate that CD26 expression may identify subsets of B-CLL patients with an unfavourable clinical outcome in terms of therapeutic need, thus suggesting its potential role as a marker (together with CD38 and CD49d) in a future routine cytofluorimetric panel to be validated for the prognostic stratification of B-CLLs.

CD62L as a Therapeutic Target in Chronic Lymphocytic Leukemia

“…Interaction between B cells and T h cells in lymph node proliferating centres is mediated via CD40 crosslinking with CD40L to activate protein kinases such as Lyn and Syk and such interactions have been observed in CLL patient lymph nodes (28). The fact that CD26 was increased in surviving CLL cells is indicative of B-cell activation (29,30), which is consistent with the upregulation of CD58, another marker of costimulation. It has been shown that incubation of CLL cells with human CD40L-expressing T cells results in increased CD54, CD58, CD80, and CD86 (31).…”

Accelerated progression of chronic lymphocytic leukemia in Eμ-TCL1 mice expressing catalytically inactive RAG1

“…For example, both Dpp4 upregulation and Sell downregulation reportedly correlate with poor prognosis in human CLL, 44,45 which is consistent with the earlier onset of disease observed in DTG mice relative to Em-TCL1 mice. However, we cannot exclude the possible contribution of T cells in accelerating disease progression in DTG mice because T cells have been implicated in CLL development in Em-TCL1 mice, 46,47 and splenic T cells in DTG mice are quantitatively elevated compared with both dnRAG1 and Em-TCL1 mice at 36 weeks.…”

Expression and prognostic assessment of dipeptidyl peptidase IV and related enzymes in B-cell chronic lymphocytic leukemia

“…This is in part contradictory to a number of published studies. [48][49][50] The microarray study of Klein et al identified high CD26 expression as being associated with an un-mutated IgVH mutational status (5.6-fold upregulation compared to mutated CLL cases) (n = 16). Although no further validation or discussion of this finding was undertaken in their study, their finding corresponds to the recent study of Cro et al who also found high CD26 expression (>10% CD26 positive cells, identical to the cut-off used in this study) to be associated with an un-mutated IgVH mutational status and high CD49d expression in a study of 112 CLL patients.…”