Bibliographic Details
| Title: |
Protein Kinase CK2 represents a new target to boost Ibrutinib and Venetoclax induced cytotoxicity in mantle cell lymphoma |
| Authors: |
Sabrina Manni, Maria Pesavento, Zaira Spinello, Lara Saggin, Arash Arjomand, Anna Fregnani, Laura Quotti Tubi, Greta Scapinello, Carmela Gurrieri, Gianpietro Semenzato, Livio Trentin, Francesco Piazza |
| Source: |
Frontiers in Cell and Developmental Biology, Vol 10 (2022) |
| Publisher Information: |
Frontiers Media S.A., 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
mantle cell lymphoma, CK2, ibrutinib, venetoclax, target therapy, Biology (General), QH301-705.5 |
| More Details: |
Mantle cell lymphoma (MCL) is an incurable B cell non-Hodgkin lymphoma, characterized by frequent relapses. In the last decade, the pro-survival pathways related to BCR signaling and Bcl-2 have been considered rational therapeutic targets in B cell derived lymphomas. The BTK inhibitor Ibrutinib and the Bcl-2 inhibitor Venetoclax are emerging as effective drugs for MCL. However, primary and acquired resistance also to these agents may occur. Protein Kinase CK2 is a S/T kinase overexpressed in many solid and blood-derived tumours. CK2 promotes cancer cell growth and clonal expansion, sustaining pivotal survival signaling cascades, such as the ones dependent on AKT, NF-κB, STAT3 and others, counteracting apoptosis through a “non-oncogene” addiction mechanism. We previously showed that CK2 is overexpressed in MCL and regulates the levels of activating phosphorylation on S529 of the NF-κB family member p65/RelA. In the present study, we investigated the effects of CK2 inactivation on MCL cell proliferation, survival and apoptosis and this kinase’s involvement in the BCR and Bcl-2 related signaling. By employing CK2 loss of function MCL cell models, we demonstrated that CK2 sustains BCR signaling (such as BTK, NF-κB and AKT) and the Bcl-2-related Mcl-1 expression. CK2 inactivation enhanced Ibrutinib and Venetoclax-induced cytotoxicity. The demonstration of a CK2-dependent upregulation of pathways that may antagonize the effect of these drugs may offer a novel strategy to overcome primary and secondary resistance. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2296-634X |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fcell.2022.935023/full; https://doaj.org/toc/2296-634X |
| DOI: |
10.3389/fcell.2022.935023 |
| Access URL: |
https://doaj.org/article/4e50422512014aa7a3dad54cf148b427 |
| Accession Number: |
edsdoj.4e50422512014aa7a3dad54cf148b427 |
| Database: |
Directory of Open Access Journals |
