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Azzolini 2016 Abstract Mito Xmas Meeting Innsbruck
Diseases Cancer  +
Event Poster  +
Has abstract 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.  +
Has title Targeting a mitochondrial potassium channel as a new way to treat chronic lymphocytic leukemia.  +
Mammal and model Human  + , Mouse  +
MiP area Pharmacology;toxicology  +
Stress Cell death  +
Tissue and cell Lymphocyte  +
Was submitted in year 2016  +
Was submitted to event Mito Xmas Meeting 2016 Innsbruck AT +
Was written by Azzolini M + , Martini V + , Severin F + , Romio M + , Mattarei A + , Zoratti M + , Trentin L + , Semenzato G + , Paradisi C + , Leanza L + , Szabo I +
Categories Abstracts
Modification date
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10:35:54, 14 December 2016  +
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