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Disease-inducing potential of two leukemic cell lines in a xenografting model

  • Fertility Preservation
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Cryopreserved ovarian tissue transplant restores ovarian function in young cancer patients after gonadotoxic treatment. However, leukemia is associated with increased risk of malignant cell transmission. We aimed to assess the tumor-inducing potential of two different leukemic cell lines when xenografted to immunodeficient mice.

Methods

Fifty-four female immunodeficient mice were grafted with either 100, 200, 500, 1000, and 10,000 chronic myeloid leukemia in blast crisis (BV-173) cells or relapsed acute lymphoblastic leukemia (RCH-ACV) cells, embedded inside a fibrin scaffold along with 50,000 human ovarian stromal cells. Two mice per cell line received the fibrin matrix without leukemic cells as negative controls. Clinical signs of disease were monitored for 20 weeks. Grafts, liver tissue, and masses were collected for macroscopic analysis and gene expression of BCR-ABL1 and E2A-PBX fusion transcripts present in BV-173 and RCH-ACV respectively.

Results

BV-173 cells: Mice grafted with 100, 200, or 500 cells showed no sign of disease after and were negative for BCR-ABL1 expression. Three of the 5 animals grafted with 1000 cells and all mice with 10,000 cells developed disease and showed BCR-ABL1-positive expression. RCH-ACV cells: Two out of 4 mice grafted with 100 cells developed disease and were E2A-PBX1-positive. All the animals grafted with higher cell doses showed signs of disease and all but one were E2A-PBX1-positive.

Conclusion

The present work proves that the disease-inducing potential of BV-173 and RCH-ACV leukemic cells xenografted to SCID mouse peritoneum differs between cell lines, depending on cell number, type, status, and cytogenetic disease profile when ovarian tissue is harvested.

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Acknowledgements

The authors thank Mira Hryniuk, BA, for reviewing the English language of the manuscript, and Dolores Gonzalez for her technical assistance.

Funding

This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique, FNRS-PDR Convention T.0077.14, Télévie grant No. 7.6515.16F awarded to DDM and grant 5/4/150/5 awarded to MMD, Fonds Spéciaux de Recherche, Fondation St Luc, and Foundation Against Cancer, and donations from the Ferrero family. This study was also funded by the Regional Valencian Ministry of Education (PROMETEO/2018/137) and the Spanish Ministry of Science and Innovation (CP19/00141 for S.H. participation).

Author information

Authors and Affiliations

  1. Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Mounier 52, bte. B1.52.02, 1200, Brussels, Belgium

    D. D. Manavella, M. Soares & M. M. Dolmans

  2. Neolife-Medicina y Cirugía Reproductiva, Brasilia 760, 1434, Asunción, Paraguay

    D. D. Manavella

  3. IVI Foundation-Instituto de Investigación Sanitaria Hospital La Fe (IIS La Fe), Valencia, Spain

    Sonia Herraiz, A. Buigues, A. Pellicer & C. Díaz-García

  4. Society for Research into Infertility, Brussels, Belgium

    J. Donnez

  5. IVI London, IVIRMA Global, London, W1G 9RQ, UK

    C. Díaz-García

  6. Department of Reproductive Health, UCL, London, WC1E 6AU, UK

    C. Díaz-García

  7. Gynecology Department, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium

    M. M. Dolmans

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  1. D. D. Manavella
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  2. Sonia Herraiz
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  3. M. Soares
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Contributions

DDM: performed PCR for the BV-173 cell line, interpreted results, and wrote the manuscript. SH: performed all experiments and PCR analyses for the RCH-ACV cell line, interpreted results, and revised the manuscript. MS: carried out experimental procedures for the BV-173 cell line. AB: performed surgery, PCR, and histological analysis for the RCH-ACV cell line. JD: prepared and revised the manuscript. AP: revised the manuscript. CDG: designed the study, interpreted results, and revised the manuscript. MMD: designed the study, performed experimental procedures, and revised the manuscript.

Corresponding author

Correspondence to Sonia Herraiz.

Ethics declarations

Ethics approval

The use of human tissue for this study was approved by the Institutional Review Board of both the Université Catholique de Louvain (2012/23MAR/125) and La Fe University Hospital (2011/0018). Animal welfare guidelines were approved by the Committee on Animal Research of both the Université Catholique de Louvain (2014/UCL/M.D./007) and the University of Valencia (Ref. 2015/VSC/PEA/0013).

Conflict of interest

The authors declare no competing interests.

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Manavella D. D. and Herraiz S. should be considered similar in author order.

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Manavella, D.D., Herraiz, S., Soares, M. et al. Disease-inducing potential of two leukemic cell lines in a xenografting model. J Assist Reprod Genet 38, 1589–1600 (2021). https://doi.org/10.1007/s10815-021-02169-2

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  • DOI: https://doi.org/10.1007/s10815-021-02169-2

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