Pharmacological inhibition of carbonic anhydrase XII interferes with cell proliferation and induces cell apoptosis in T-cell lymphomas

The membrane-bound carbonic anhydrase isoforms CAIX and CAXII, underpin a pH-regulating system that enables hypoxic tumor cell survival. Here, we observed for the first time an upregulation of CAXII in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LL) cells. First we showed that CAXII is overexpressed in thymocytes from tPTEN−/− mice suffering of T lymphoma and that its pharmacological inhibition decreased cell proliferation and induced apoptosis. The same results were observed with the SupT1 human T cell lymphoma line. In addition we observed an upregulation of CAXII in human T-ALL samples supporting the case that CAXII may represent a new therapeutic target for T-ALL/LL.

► We described for the first time expression of carbonic anhydrase XII in T-ALL/LL. ► CAXII inhibitors decrease cell proliferation and induce cell death of T lymphoma cell lines. ► CAXII inhibitors induce cell death of primary lymphocytes from human T-ALL samples. ► Targeting CAXII in T-ALL may represent a new therapeutic window for T-ALL/LL.