CD26 Expression Correlates with a Reduced Sensitivity to 2′-Deoxycoformycin-Induced Growth Inhibition and Apoptosis in T-Cell Leukemia/Lymphomas

Abstract

Purpose and Experimental Design: dCF (2 -deoxycoformycin) is a potent inhibitor of ADA (adenosine deaminase), an enzyme regulating intra-and extracellular concentrations of purine metabolites. ADA exists as cytosolic and extracellular forms, the latter colocalized on the cell surface with CD26. Once the surface expression of CD26 and ADA in a panel of cell lines and primary samples of T-cell leukemia/lymphoma was defined, we correlated this expression with the antiproliferative and apoptotic effect of dCF.Results: Surface expression of CD26 inversely correlated with the capability of dCF to inhibit cell growth and induce apoptosis both in T-cell lines and primary samples of T-cell malignancies. This conclusion was sustained by a decreased sensitivity to dCF-mediated proapoptotic and/or antiproliferative in vitro effects of: (a) leukemia/lymphoma T-cell lines expressing surface CD26/ADA complex; (b) primary CD26 ؉ T cell malignancies; and (c) normal T cells (CD26 ؉ ) as compared with tumor T cells (CD26 ؊ ) in unpurified samples from three cases of T-cell receptor ␥␦ ؉ T-cell malignancies characterized by a mixture of normal and neoplastic cells. This latter point was confirmed in vivo, in a patient affected by CD26 ؊ T-cell receptor ␥␦ ؉ hepatosplenic ␥␦ ؉ T-cell lymphomas treated on a compassionate basis with dCF. The inverse correlation between CD26 expression and sensitivity to dCF was also demonstrated in a lymphoblastic lymphoma case in which CD26 was expressed on circulating blasts at relapse but not at diagnosis, as well as in two H9 T-cell clones expressing or not expressing CD26 mRNA and protein.Conclusions: This study corroborates the notion of CD26 as a marker of poor prognosis for T-cell malignancies and delineates a role for CD26 as a predictor of poor response to dCF.

Immunologic pathomechanism of Hodgkin's lymphoma

“…It induces proinflammatory cytokine production, but it does not affect Tregs; therefore, its cytotoxic effect is not significant. Pentostatin also specifically targets CD4 þ CD26 -T cells in the microenvironment, leading to a decrease in numbers [102,103]. Gemcitabine is commonly used to treat relapsed HL; it inhibits immunosuppressing cells, thus modifying the immunologic properties of the microenvironment [104].…”

Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line

“…Cellular Proliferation and Apoptosis. DPIV expression can influence cell proliferation and apoptosis [32][33][34][35] but no such data on FAP are available. The thymidine uptake assay detected robust 293T cell proliferation, in the range 5,000 to 15,000 cpm in 5 experiments.…”

CD26: A Prognostic Marker of Acute Lymphoblastic Leukemia in Children in the Post Remission Induction Phase

“…Serum CD26 levels are an important emerging marker of B-cell chronic lymphocytic leukaemia (Cro et al, 2009).Other study showed that the first treatment in B-CLL which display higher serum CD26 levels (Molica, 2009), CD26 serves as a marker of poor prognosis in T cell lymphomas CD26 (Aldinucci et al, 2004).Another study described that CD26 expression is found mainly in aggressive subtypes of non-Hodgkin's lymphomas for example T-lymphoblastic lymphoma (LBL)/T-ALL (Carbone et al, 1995). Other work also demonstrated an enhancement in the expression of CD26 in cases of T cell acute lymphoblastic leukemia, the majority of patients with T-ALL were found to express CD26 on the tumor cell surface, with a strong correlation noted between CD26 expression and the presence of DPPIV enzyme activity in the Tlymphoblasts (Klobusicka et al, 1999).…”