Meta-Analysis Reveals Significant Sex Differences in Chronic Lymphocytic Leukemia Progression in the <i>Eµ-TCL1</i> Transgenic Mouse Model

Maximilian Koch; Sebastian Reinartz; Julia Saggau; Gero Knittel; Natascha Rosen; Oleg Fedorchenko; Lisa Thelen; Romy Barthel; Nina Reinart; Tamina Seeger-Nukpezah; Hans Christian Reinhardt; Michael Hallek; Phuong-Hien Nguyen

doi:10.3390/cancers12071980

Cancers (Jul 2020)

Meta-Analysis Reveals Significant Sex Differences in Chronic Lymphocytic Leukemia Progression in the <i>Eµ-TCL1</i> Transgenic Mouse Model

Maximilian Koch,
Sebastian Reinartz,
Julia Saggau,
Gero Knittel,
Natascha Rosen,
Oleg Fedorchenko,
Lisa Thelen,
Romy Barthel,
Nina Reinart,
Tamina Seeger-Nukpezah,
Hans Christian Reinhardt,
Michael Hallek,
Phuong-Hien Nguyen

Affiliations

Maximilian Koch: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Sebastian Reinartz: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Julia Saggau: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Gero Knittel: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Natascha Rosen: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Oleg Fedorchenko: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Lisa Thelen: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Romy Barthel: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Nina Reinart: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Tamina Seeger-Nukpezah: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Hans Christian Reinhardt: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Michael Hallek: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany
Phuong-Hien Nguyen: University of Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Center for Molecular Medicine Cologne, CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, 50931 Cologne, Germany

DOI: https://doi.org/10.3390/cancers12071980
Journal volume & issue: Vol. 12, no. 7
p. 1980

Abstract

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The Eµ-TCL1 transgenic mouse model represents the most widely and extensively used animal model for chronic lymphocytic leukemia (CLL). In this report, we performed a meta-analysis of leukemia progression in over 300 individual Eµ-TCL1 transgenic mice and discovered a significantly accelerated disease progression in females compared to males. This difference is also reflected in an aggressive CLL mouse model with additional deletion of Tp53 besides the TCL1 transgene. Moreover, after serial adoptive transplantation of murine CLL cells, female recipients also succumbed to CLL earlier than male recipients. This sex-related disparity in the murine models is markedly contradictory to the human CLL condition. Thus, due to our observation we urge both careful consideration in the experimental design and accurate description of the Eµ-TCL1 transgenic cohorts in future studies.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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