Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Thinking Outside the Box: Indirect Myc Modulation in Canine B-Cell Lymphoma

Luca Licenziato
ORCID logo ,
Eugenio Mazzone
ORCID logo ,
Chiara Tarantelli
ORCID logo ,
Paolo Accornero
,
Andrea Rinaldi
,
Sara Divari
ORCID logo ,
Wilfred Leung
,
Suzin Webb
,
Raffaella De Maria
,
Luca Aresu
* ORCID logo
Version 1 : Received: 27 April 2024 / Approved: 28 April 2024 / Online: 28 April 2024 (08:39:00 CEST)

How to cite: Licenziato, L.; Mazzone, E.; Tarantelli, C.; Accornero, P.; Rinaldi, A.; Divari, S.; Leung, W.; Webb, S.; De Maria, R.; Aresu, L. Thinking Outside the Box: Indirect Myc Modulation in Canine B-Cell Lymphoma. Preprints 2024, 2024041830. https://doi.org/10.20944/preprints202404.1830.v1 Licenziato, L.; Mazzone, E.; Tarantelli, C.; Accornero, P.; Rinaldi, A.; Divari, S.; Leung, W.; Webb, S.; De Maria, R.; Aresu, L. Thinking Outside the Box: Indirect Myc Modulation in Canine B-Cell Lymphoma. Preprints 2024, 2024041830. https://doi.org/10.20944/preprints202404.1830.v1

Abstract

B-cell lymphomas (BCL) is the most frequent hematological cancer in dogs. Treatment typically consists of chemotherapy, with CHOP-based protocols. However, outcome remains generally poor, urging the exploration of new therapeutic strategies with a targeted approach. Myc tran-scription factor plays a crucial role in regulating cellular processes and its dysregulation is im-plicated in numerous human and canine malignancies, including canine BCL (cBCL). This study aims to evaluate the efficacy of indirectly inhibiting Myc in cBCL using BI2536 and MZ1 com-pounds in two in vitro models (CLBL-1 and KLR-1201). Both BI2536 and MZ1, alone and com-bined, affected cell viability in a significant concentration and time-dependent manner. Western Blot revealed an upregulation of PLK1 expression in both cell lines upon treatment with BI2536, in association with a reduction in c-Myc protein levels. Conversely, MZ1 led to a decrease in its primary target, BRD4, along with a reduction in c-Myc. Furthermore, BI2536, both alone and in combination with MZ1, induced larger transcriptomic changes in cells compared to MZ1 alone, primarily affecting MYC target genes and genes involved in cell cycle regulation. These data un-derscore the potential role of Myc as therapeutic target in cBCL, providing a novel approach to indirectly modulate this molecule.

Keywords

canine B-cell lymphoma; targeted therapy; Myc; BI2536; MZ1

Subject

Medicine and Pharmacology, Veterinary Medicine

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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