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Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway

PURPOSE: Is it possible to eliminate metastasised chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells from ovarian cortex fragments by inhibition of Aurora B/C kinases (AURKB/C) without compromising ovarian tissue or follicles? METHODS: Human ovarian cortex tissue with experiment...

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Autores principales: Eijkenboom, Lotte, Mulder, Callista, van der Reijden, Bert, van Mello, Norah, van Leersum, Julia, Koorenhof-Scheele, Thessa, Braat, Didi, Beerendonk, Catharina, Peek, Ronald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266964/
https://www.ncbi.nlm.nih.gov/pubmed/33725274
http://dx.doi.org/10.1007/s10815-021-02081-9
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author Eijkenboom, Lotte
Mulder, Callista
van der Reijden, Bert
van Mello, Norah
van Leersum, Julia
Koorenhof-Scheele, Thessa
Braat, Didi
Beerendonk, Catharina
Peek, Ronald
author_facet Eijkenboom, Lotte
Mulder, Callista
van der Reijden, Bert
van Mello, Norah
van Leersum, Julia
Koorenhof-Scheele, Thessa
Braat, Didi
Beerendonk, Catharina
Peek, Ronald
author_sort Eijkenboom, Lotte
collection PubMed
description PURPOSE: Is it possible to eliminate metastasised chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells from ovarian cortex fragments by inhibition of Aurora B/C kinases (AURKB/C) without compromising ovarian tissue or follicles? METHODS: Human ovarian cortex tissue with experimentally induced tumour foci of CML, AML and primary cells of AML patients were exposed to a 24h treatment with 1 μM GSK1070916, an AURKB/C inhibitor, to eliminate malignant cells by invoking mitotic catastrophe. After treatment, the inhibitor was removed, followed by an additional culture period of 6 days to allow any remaining tumour cells to form new foci. Ovarian tissue integrity after treatment was analysed by four different assays. Appropriate controls were included in all experiments. RESULTS: Foci of metastasised CML and AML cells in ovarian cortex tissue were severely affected by a 24h ex vivo treatment with an AURKB/C inhibitor, leading to the formation of multi-nuclear syncytia and large-scale apoptosis. Ovarian tissue morphology and viability was not compromised by the treatment, as no significant difference was observed regarding the percentage of morphologically normal follicles, follicular viability, glucose uptake or in vitro growth of small follicles between ovarian cortex treated with 1 μM GSK1070916 and the control. CONCLUSION: Purging of CML/AML metastases in ovarian cortex is possible by targeting the Mitotic Catastrophe Signalling Pathway using GSK1070916 without affecting the ovarian tissue. This provides a therapeutic strategy to prevent reintroduction of leukaemia and enhances safety of autotransplantation in leukaemia patients currently considered at high risk for ovarian involvement. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02081-9.
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spelling pubmed-82669642021-07-20 Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway Eijkenboom, Lotte Mulder, Callista van der Reijden, Bert van Mello, Norah van Leersum, Julia Koorenhof-Scheele, Thessa Braat, Didi Beerendonk, Catharina Peek, Ronald J Assist Reprod Genet Fertility Preservation PURPOSE: Is it possible to eliminate metastasised chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells from ovarian cortex fragments by inhibition of Aurora B/C kinases (AURKB/C) without compromising ovarian tissue or follicles? METHODS: Human ovarian cortex tissue with experimentally induced tumour foci of CML, AML and primary cells of AML patients were exposed to a 24h treatment with 1 μM GSK1070916, an AURKB/C inhibitor, to eliminate malignant cells by invoking mitotic catastrophe. After treatment, the inhibitor was removed, followed by an additional culture period of 6 days to allow any remaining tumour cells to form new foci. Ovarian tissue integrity after treatment was analysed by four different assays. Appropriate controls were included in all experiments. RESULTS: Foci of metastasised CML and AML cells in ovarian cortex tissue were severely affected by a 24h ex vivo treatment with an AURKB/C inhibitor, leading to the formation of multi-nuclear syncytia and large-scale apoptosis. Ovarian tissue morphology and viability was not compromised by the treatment, as no significant difference was observed regarding the percentage of morphologically normal follicles, follicular viability, glucose uptake or in vitro growth of small follicles between ovarian cortex treated with 1 μM GSK1070916 and the control. CONCLUSION: Purging of CML/AML metastases in ovarian cortex is possible by targeting the Mitotic Catastrophe Signalling Pathway using GSK1070916 without affecting the ovarian tissue. This provides a therapeutic strategy to prevent reintroduction of leukaemia and enhances safety of autotransplantation in leukaemia patients currently considered at high risk for ovarian involvement. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02081-9. Springer US 2021-03-16 2021-06 /pmc/articles/PMC8266964/ /pubmed/33725274 http://dx.doi.org/10.1007/s10815-021-02081-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Fertility Preservation
Eijkenboom, Lotte
Mulder, Callista
van der Reijden, Bert
van Mello, Norah
van Leersum, Julia
Koorenhof-Scheele, Thessa
Braat, Didi
Beerendonk, Catharina
Peek, Ronald
Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway
title Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway
title_full Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway
title_fullStr Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway
title_full_unstemmed Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway
title_short Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway
title_sort purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway
topic Fertility Preservation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266964/
https://www.ncbi.nlm.nih.gov/pubmed/33725274
http://dx.doi.org/10.1007/s10815-021-02081-9
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