Azzolini 2016 Abstract Mito Xmas Meeting Innsbruck: Difference between revisions
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{{Abstract | {{Abstract | ||
|title=Targeting a mitochondrial potassium channel as a new | |title=Targeting a mitochondrial potassium channel as a new way to treat chronic lymphocytic leukemia. | ||
|authors=Azzolini M, Martini V, Severin F, Romio M, Mattarei A, Zoratti M, Trentin L, Semenzato G, Paradisi C, Leanza L, Szabo I | |||
|authors=Azzolini M, Martini V, Severin F, Romio M, Mattarei A, Zoratti M, Trentin L, Semenzato G, Paradisi C, Leanza L, | |||
|year=2016 | |year=2016 | ||
|event=Mito Xmas Meeting 2016 Innsbruck AT | |event=Mito Xmas Meeting 2016 Innsbruck AT | ||
|abstract=Human Chronic Lymphocytic Leukemia (B-CLL) is the most commonly diagnosed leukemia in the | |abstract=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. | ||
|editor=[[Gnaiger E]], | |||
| | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Pharmacology;toxicology | |||
|diseases=Cancer | |||
|injuries=Cell death | |||
|organism=Human, Mouse | |||
|tissues=Lymphocyte | |||
|event=Poster | |event=Poster | ||
|additional=Leukemia, | |||
}} | }} | ||
== Affiliations == | == Affiliations == | ||
Line 19: | Line 23: | ||
::::# Dept Biomedical Sc, Univ Padua, Italy | ::::# Dept Biomedical Sc, Univ Padua, Italy | ||
::::# Dept Chemical Sc, Univ Padua, Italy | ::::# Dept Chemical Sc, Univ Padua, Italy | ||
::::# Dept Medicine, Hematology Immunological Branch, Univ Padova, Venetian Inst for Molecular Medicine (VIMM), | ::::# Dept Medicine, Hematology Immunological Branch, Univ Padova, Venetian Inst for Molecular Medicine (VIMM), Padova, Italy | ||
::::# Dept Biology, Univ Padua, Italy | ::::# Dept Biology, Univ Padua, Italy |
Latest revision as of 18:28, 31 January 2020
Targeting a mitochondrial potassium channel as a new way to treat chronic lymphocytic leukemia. |
Link:
Azzolini M, Martini V, Severin F, Romio M, Mattarei A, Zoratti M, Trentin L, Semenzato G, Paradisi C, Leanza L, Szabo I (2016)
Event: Mito Xmas Meeting 2016 Innsbruck AT
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.
• Bioblast editor: Gnaiger E
Labels: MiParea: Pharmacology;toxicology Pathology: Cancer Stress:Cell death Organism: Human, Mouse Tissue;cell: Lymphocyte
Event: Poster
Leukemia
Affiliations
- Azzolini M(1,2), Martini V(3), Severin F(3), Romio M(4), Mattarei A(4), Zoratti M(1,2), Trentin L(3), Semenzato G(3), Paradisi C(4), Leanza L(5), Szabò I(1,5)
- CNR Inst Neurosciences, Padua, Italy
- Dept Biomedical Sc, Univ Padua, Italy
- Dept Chemical Sc, Univ Padua, Italy
- Dept Medicine, Hematology Immunological Branch, Univ Padova, Venetian Inst for Molecular Medicine (VIMM), Padova, Italy
- Dept Biology, Univ Padua, Italy