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- Azzolini 2016 Abstract Mito Xmas Meeting Innsbruck + (Human Chronic Lymphocytic Leukemia (B-CLL) … Human Chronic Lymphocytic Leukemia (B-CLL) is the most commonly diagnosed leukemia in the western world. Therapeutic options to treat this leukemia are very limited. B-CLL is characterized by a clonal accumulation of mature neoplastic B cells that are resistant to apoptosis. Different leukemic cells or cell lines, both myeloid and lymphoid, express/overexpress several potassium channels including shaker type voltage-gated Kv1.3, Kv11.1 (Herg), and calcium-activated KCa3.1, and their pharmacological inhibition has been related to reduced B-CLL proliferation, pointing to ion channels as promising oncological targets in B-CLL. We obtained evidence that Kv1.3 is highly expressed in B-CLL respect to normal B cells both in the plasma membrane and in the inner mitochondrial membrane. We have recently shown that the treatment with mitochondrial Kv1.3 inhibitors actively killed primary B-CLL cells in ''ex-vivo'' experiments, by induction of intrinsic apoptosis. Importantly, cells form healthy subjects and even residual normal T lymphocytes of the same patients were unaffected by the drugs, while B-CLL cells were killed. Importantly, B-CLL cell death was observed also when leukemic cells were co-cultured with mesenchymal stromal cells (MSC), which favor tumor cell growth by releasing anti-apoptotic and pro-survival factors. Here we report the first ''in vivo'' evidence, that pharmacological targeting of the mitochondrial Kv1.3 by a new mitochondrial targeted inhibitor is sufficient to lead to a massive CD5+/CD19+ elimination in several organs (blood, peritoneal cavity, spleen, bone marrow) in a B-CLL genetic mouse model (EuTCL-1), without inducing side effects and death in healthy immune cells, including cytotoxic T lymphocytes. These results open the possibility to a new therapeutical approach for this disease by directly targeting the mitochondrial channel.ectly targeting the mitochondrial channel.)