Dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.

Current chemotherapy for treatment of pediatric acute leukemia, although generally successful, is still a matter of concern due to treatment resistance, relapses and life-long side effects for a subset of patients. Inhibition of dynamin, a GTPase involved in clathrin-mediated endocytosis and regulat...

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Autores principales:	Christopher von Beek, Linnéa Alriksson, Josefine Palle, Ann-Marie Gustafson, Mirjana Grujic, Fabio Rabelo Melo, Mikael E Sellin, Gunnar Pejler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b614d18e45a4f0386467264e671f2aa
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spelling	oai:doaj.org-article:5b614d18e45a4f0386467264e671f2aa2021-12-02T20:08:27ZDynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.1932-620310.1371/journal.pone.0256708https://doaj.org/article/5b614d18e45a4f0386467264e671f2aa2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256708https://doaj.org/toc/1932-6203Current chemotherapy for treatment of pediatric acute leukemia, although generally successful, is still a matter of concern due to treatment resistance, relapses and life-long side effects for a subset of patients. Inhibition of dynamin, a GTPase involved in clathrin-mediated endocytosis and regulation of the cell cycle, has been proposed as a potential anti-cancer regimen, but the effects of dynamin inhibition on leukemia cells has not been extensively addressed. Here we adopted single cell and whole-population analysis by flow cytometry and live imaging, to assess the effect of dynamin inhibition (Dynasore, Dyngo-4a, MitMAB) on pediatric acute leukemia cell lines (CCRF-CEM and THP-1), human bone marrow biopsies from patients diagnosed with acute lymphoblastic leukemia (ALL), as well as in a model of lymphoma (EL4)-induced tumor growth in mice. All inhibitors suppressed proliferation and induced pronounced caspase-dependent apoptotic cell death in CCRF-CEM and THP-1 cell lines. However, the inhibitors showed no effect on bone marrow biopsies, and did not prevent EL4-induced tumor formation in mice. We conclude that dynamin inhibition affects highly proliferating human leukemia cells. These findings form a basis for evaluation of the potential, and constraints, of employing dynamin inhibition in treatment strategies against leukemia and other malignancies.Christopher von BeekLinnéa AlrikssonJosefine PalleAnn-Marie GustafsonMirjana GrujicFabio Rabelo MeloMikael E SellinGunnar PejlerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0256708 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christopher von Beek Linnéa Alriksson Josefine Palle Ann-Marie Gustafson Mirjana Grujic Fabio Rabelo Melo Mikael E Sellin Gunnar Pejler Dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.
description	Current chemotherapy for treatment of pediatric acute leukemia, although generally successful, is still a matter of concern due to treatment resistance, relapses and life-long side effects for a subset of patients. Inhibition of dynamin, a GTPase involved in clathrin-mediated endocytosis and regulation of the cell cycle, has been proposed as a potential anti-cancer regimen, but the effects of dynamin inhibition on leukemia cells has not been extensively addressed. Here we adopted single cell and whole-population analysis by flow cytometry and live imaging, to assess the effect of dynamin inhibition (Dynasore, Dyngo-4a, MitMAB) on pediatric acute leukemia cell lines (CCRF-CEM and THP-1), human bone marrow biopsies from patients diagnosed with acute lymphoblastic leukemia (ALL), as well as in a model of lymphoma (EL4)-induced tumor growth in mice. All inhibitors suppressed proliferation and induced pronounced caspase-dependent apoptotic cell death in CCRF-CEM and THP-1 cell lines. However, the inhibitors showed no effect on bone marrow biopsies, and did not prevent EL4-induced tumor formation in mice. We conclude that dynamin inhibition affects highly proliferating human leukemia cells. These findings form a basis for evaluation of the potential, and constraints, of employing dynamin inhibition in treatment strategies against leukemia and other malignancies.
format	article
author	Christopher von Beek Linnéa Alriksson Josefine Palle Ann-Marie Gustafson Mirjana Grujic Fabio Rabelo Melo Mikael E Sellin Gunnar Pejler
author_facet	Christopher von Beek Linnéa Alriksson Josefine Palle Ann-Marie Gustafson Mirjana Grujic Fabio Rabelo Melo Mikael E Sellin Gunnar Pejler
author_sort	Christopher von Beek
title	Dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.
title_short	Dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.
title_full	Dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.
title_fullStr	Dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.
title_full_unstemmed	Dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.
title_sort	dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5b614d18e45a4f0386467264e671f2aa
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Dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.

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