https://wiki.oroboros.at/index.php?title=Machado-Neto_2018_Cell_Death_Dis&feed=atom&action=history
Machado-Neto 2018 Cell Death Dis - Revision history
2024-03-28T11:46:20Z
Revision history for this page on the wiki
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https://wiki.oroboros.at/index.php?title=Machado-Neto_2018_Cell_Death_Dis&diff=215135&oldid=prev
Komlodi Timea at 15:17, 8 February 2021
2021-02-08T15:17:50Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 15:17, 8 February 2021</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F (2018) Metformin exerts multitarget antileukemia activity in JAK2<sup>V617F</sup>-positive myeloproliferative neoplasms. Cell Death Dis 9:311.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F (2018) Metformin exerts multitarget antileukemia activity in JAK2<sup>V617F</sup>-positive myeloproliferative neoplasms. Cell Death Dis 9:311.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29472557 PMID: 29472557 Open Access]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29472557 PMID: 29472557 Open Access]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|authors=Machado-Neto <del style="font-weight: bold; text-decoration: none;">JA</del>, Fenerich <del style="font-weight: bold; text-decoration: none;">BA</del>, Scopim-Ribeiro <del style="font-weight: bold; text-decoration: none;">R</del>, Eide <del style="font-weight: bold; text-decoration: none;">CA</del>, Coelho-Silva <del style="font-weight: bold; text-decoration: none;">JL</del>, Dechandt <del style="font-weight: bold; text-decoration: none;">CRP</del>, Fernandes <del style="font-weight: bold; text-decoration: none;">JC</del>, Rodrigues Alves <del style="font-weight: bold; text-decoration: none;">APN</del>, Scheucher <del style="font-weight: bold; text-decoration: none;">PS</del>, Simoes <del style="font-weight: bold; text-decoration: none;">BP</del>, Alberici Luciane Carla, de Figueiredo Pontes <del style="font-weight: bold; text-decoration: none;">LL</del>, Tognon <del style="font-weight: bold; text-decoration: none;">CE</del>, Druker <del style="font-weight: bold; text-decoration: none;">BJ</del>, Rego <del style="font-weight: bold; text-decoration: none;">EM</del>, Traina <del style="font-weight: bold; text-decoration: none;">F</del></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|authors=Machado-Neto <ins style="font-weight: bold; text-decoration: none;">João Agostinho</ins>, Fenerich <ins style="font-weight: bold; text-decoration: none;">Bruna Alves</ins>, Scopim-Ribeiro <ins style="font-weight: bold; text-decoration: none;">Renata</ins>, Eide <ins style="font-weight: bold; text-decoration: none;">Christopher A</ins>, Coelho-Silva <ins style="font-weight: bold; text-decoration: none;">Juan Luiz</ins>, Dechandt <ins style="font-weight: bold; text-decoration: none;">Carlos Roberto Porto</ins>, Fernandes <ins style="font-weight: bold; text-decoration: none;">Jaqueline Cristina</ins>, Rodrigues Alves <ins style="font-weight: bold; text-decoration: none;">Ana Paula Nunes</ins>, Scheucher <ins style="font-weight: bold; text-decoration: none;">Priscila Santos</ins>, Simoes <ins style="font-weight: bold; text-decoration: none;">Belinda Pinto</ins>, Alberici Luciane Carla, de Figueiredo Pontes <ins style="font-weight: bold; text-decoration: none;">Lorena Lobo</ins>, Tognon <ins style="font-weight: bold; text-decoration: none;">Cristina E</ins>, Druker <ins style="font-weight: bold; text-decoration: none;">Brian J</ins>, Rego <ins style="font-weight: bold; text-decoration: none;">Eduardo Magalhaes</ins>, Traina <ins style="font-weight: bold; text-decoration: none;">Fabiola</ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2018</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2018</div></td></tr>
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Komlodi Timea
https://wiki.oroboros.at/index.php?title=Machado-Neto_2018_Cell_Death_Dis&diff=195757&oldid=prev
Gnaiger Erich at 09:16, 7 March 2020
2020-03-07T09:16:04Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 09:16, 7 March 2020</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F (2018) Metformin exerts multitarget antileukemia activity in JAK2<sup>V617F</sup>-positive myeloproliferative neoplasms. Cell Death Dis 9:311.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F (2018) Metformin exerts multitarget antileukemia activity in JAK2<sup>V617F</sup>-positive myeloproliferative neoplasms. Cell Death Dis 9:311.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29472557 PMID: 29472557 Open Access]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29472557 PMID: 29472557 Open Access]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|authors=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simoes BP, Alberici <del style="font-weight: bold; text-decoration: none;">LC</del>, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|authors=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simoes BP, Alberici <ins style="font-weight: bold; text-decoration: none;">Luciane Carla</ins>, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2018</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2018</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=Cell Death Dis</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=Cell Death Dis</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|abstract=The recurrent gain-of-function JAK2<sup>V617F</sup> mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete response in most patients treated with the JAK1/2 inhibitor ruxolitinib indicates the need for identifying novel therapeutic strategies. Metformin is a biguanide that exerts selective antineoplastic activity in hematological malignancies. In the present study, we investigate and compare effects of metformin and ruxolitinib alone and in combination on cell signaling and cellular functions in JAK2<sup>V617F</sup>-positive cells. In JAK2<sup>V617F</sup>-expressing cell lines, metformin treatment significantly reduced cell viability, cell proliferation, clonogenicity, and cellular oxygen consumption and delayed cell cycle progression. Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation. Metformin plus ruxolitinib demonstrated more intense reduction of cell viability and induction of apoptosis compared to monotherapy. Notably, metformin reduced Ba/F3 JAK2<sup>V617F</sup> tumor burden and splenomegaly in Jak2<sup>V617F</sup> knock-in-induced MPN mice and spontaneous erythroid colony formation in primary cells from polycythemia vera patients. In conclusion, metformin exerts multitarget antileukemia activity in MPN: downregulation of JAK2/STAT signaling and mitochondrial activity. Our exploratory study establishes novel molecular mechanisms of metformin and ruxolitinib action and provides insights for development of alternative/complementary therapeutic strategies for MPN.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|abstract=The recurrent gain-of-function JAK2<sup>V617F</sup> mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete response in most patients treated with the JAK1/2 inhibitor ruxolitinib indicates the need for identifying novel therapeutic strategies. Metformin is a biguanide that exerts selective antineoplastic activity in hematological malignancies. In the present study, we investigate and compare effects of metformin and ruxolitinib alone and in combination on cell signaling and cellular functions in JAK2<sup>V617F</sup>-positive cells. In JAK2<sup>V617F</sup>-expressing cell lines, metformin treatment significantly reduced cell viability, cell proliferation, clonogenicity, and cellular oxygen consumption and delayed cell cycle progression. Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation. Metformin plus ruxolitinib demonstrated more intense reduction of cell viability and induction of apoptosis compared to monotherapy. Notably, metformin reduced Ba/F3 JAK2<sup>V617F</sup> tumor burden and splenomegaly in Jak2<sup>V617F</sup> knock-in-induced MPN mice and spontaneous erythroid colony formation in primary cells from polycythemia vera patients. In conclusion, metformin exerts multitarget antileukemia activity in MPN: downregulation of JAK2/STAT signaling and mitochondrial activity. Our exploratory study establishes novel molecular mechanisms of metformin and ruxolitinib action and provides insights for development of alternative/complementary therapeutic strategies for MPN.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|editor=[[Kandolf G]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|editor=[[Kandolf G]]</div></td></tr>
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Gnaiger Erich
https://wiki.oroboros.at/index.php?title=Machado-Neto_2018_Cell_Death_Dis&diff=192578&oldid=prev
Gnaiger Erich at 02:21, 12 February 2020
2020-02-12T02:21:18Z
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Gnaiger Erich
https://wiki.oroboros.at/index.php?title=Machado-Neto_2018_Cell_Death_Dis&diff=156177&oldid=prev
Kandolf Georg at 08:38, 13 April 2018
2018-04-13T08:38:28Z
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<td colspan="2" class="diff-lineno">Line 2:</td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F (2018) Metformin exerts multitarget antileukemia activity in JAK2<sup>V617F</sup>-positive myeloproliferative neoplasms. Cell Death Dis 9:311.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F (2018) Metformin exerts multitarget antileukemia activity in JAK2<sup>V617F</sup>-positive myeloproliferative neoplasms. Cell Death Dis 9:311.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29472557 PMID: 29472557 Open Access]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29472557 PMID: 29472557 Open Access]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|authors=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, <del style="font-weight: bold; text-decoration: none;">Simões </del>BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|authors=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, <ins style="font-weight: bold; text-decoration: none;">Simoes </ins>BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2018</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2018</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=Cell Death Dis</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=Cell Death Dis</div></td></tr>
</table>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Machado-Neto_2018_Cell_Death_Dis&diff=156175&oldid=prev
Kandolf Georg: Created page with "{{Publication |title=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alber..."
2018-04-13T08:32:45Z
<p>Created page with "{{Publication |title=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alber..."</p>
<p><b>New page</b></p><div>{{Publication<br />
|title=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F (2018) Metformin exerts multitarget antileukemia activity in JAK2<sup>V617F</sup>-positive myeloproliferative neoplasms. Cell Death Dis 9:311.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29472557 PMID: 29472557 Open Access]<br />
|authors=Machado-Neto JA, Fenerich BA, Scopim-Ribeiro R, Eide CA, Coelho-Silva JL, Dechandt CRP, Fernandes JC, Rodrigues Alves APN, Scheucher PS, Simões BP, Alberici LC, de Figueiredo Pontes LL, Tognon CE, Druker BJ, Rego EM, Traina F<br />
|year=2018<br />
|journal=Cell Death Dis<br />
|abstract=The recurrent gain-of-function JAK2<sup>V617F</sup> mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete response in most patients treated with the JAK1/2 inhibitor ruxolitinib indicates the need for identifying novel therapeutic strategies. Metformin is a biguanide that exerts selective antineoplastic activity in hematological malignancies. In the present study, we investigate and compare effects of metformin and ruxolitinib alone and in combination on cell signaling and cellular functions in JAK2<sup>V617F</sup>-positive cells. In JAK2<sup>V617F</sup>-expressing cell lines, metformin treatment significantly reduced cell viability, cell proliferation, clonogenicity, and cellular oxygen consumption and delayed cell cycle progression. Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation. Metformin plus ruxolitinib demonstrated more intense reduction of cell viability and induction of apoptosis compared to monotherapy. Notably, metformin reduced Ba/F3 JAK2<sup>V617F</sup> tumor burden and splenomegaly in Jak2<sup>V617F</sup> knock-in-induced MPN mice and spontaneous erythroid colony formation in primary cells from polycythemia vera patients. In conclusion, metformin exerts multitarget antileukemia activity in MPN: downregulation of JAK2/STAT signaling and mitochondrial activity. Our exploratory study establishes novel molecular mechanisms of metformin and ruxolitinib action and provides insights for development of alternative/complementary therapeutic strategies for MPN.<br />
|editor=[[Kandolf G]]<br />
}}<br />
{{Labeling<br />
|area=Respiration, Genetic knockout;overexpression, Pharmacology;toxicology<br />
|diseases=Cancer, Other<br />
|organism=Human, Mouse<br />
|tissues=Other cell lines<br />
|preparations=Intact cells<br />
|couplingstates=LEAK, ROUTINE, ET<br />
|pathways=ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-04<br />
}}</div>
Kandolf Georg