{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T04:37:25Z","timestamp":1791693445092,"version":"4.3.4"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cell surface calcium (Ca<jats:sup>2+<\/jats:sup>) channels permit Ca<jats:sup>2+<\/jats:sup> ion influx, with Ca<jats:sup>2+<\/jats:sup> taking part in cellular functions such as proliferation, survival, and activation. The expression of voltage-dependent Ca<jats:sup>2+<\/jats:sup> (Ca<jats:sub>V<\/jats:sub>) channels may modulate the growth of hematologic cancers. Profile analysis of Ca<jats:sup>2+<\/jats:sup> channels, with a focus on the Ca<jats:sup>2+<\/jats:sup> release-activated Ca<jats:sup>2+<\/jats:sup> (CRAC) and L-type Ca<jats:sub>V<\/jats:sub> channels, was performed on RNA sequencing data from lymphoma cell lines and samples derived from patients with diffuse large B cell lymphoma (DLBCL). Ca<jats:sub>V<\/jats:sub>1.2 expression was found to be elevated in classical Hodgkin lymphoma (CHL) cell lines when compared to other B cell lymphoma cell lines. In contrast, CHL exhibited reduced expression of ORAI2 and STIM2. In our differential expression analysis comparing activated B cell-like DLBCL (ABC-DLBCL) and germinal centre B cell-like DLBCL (GCB-DLBCL) patient samples, ABC-DLBCL revealed stronger expression of Ca<jats:sub>V<\/jats:sub>1.3, whereas Ca<jats:sub>V<\/jats:sub>1.1, Ca<jats:sub>V<\/jats:sub>1.2, and Ca<jats:sub>V<\/jats:sub>1.4 showed greater expression levels in GCB-DLBCL. Interestingly, no differences in ORAI\/STIM expression were noted in the patient samples. As Ca<jats:sup>2+<\/jats:sup> is known to bind to calmodulin, leading to calcineurin activation and the passage of nuclear factor of activated T cells (NFAT) to the cell nucleus, pathways for calcineurin, calmodulin, NFAT, and Ca<jats:sup>2+<\/jats:sup> signaling were also analyzed by gene set enrichment analysis. The NFAT and Ca<jats:sup>2+<\/jats:sup> signaling pathways were found to be upregulated in the CHL cell lines relative to other B cell lymphoma cell lines. Furthermore, the calmodulin and Ca<jats:sup>2+<\/jats:sup> signaling pathways were shown to be downregulated in the ABC-DLBCL patient samples. The findings of this study suggest that L-type Ca<jats:sub>V<\/jats:sub> channels and Ca<jats:sup>2+<\/jats:sup>-related pathways could serve as differentiating components for biologic therapies in targeted lymphoma treatments.<\/jats:p>","DOI":"10.3389\/fphar.2022.795176","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T14:46:03Z","timestamp":1653403563000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Distinct Gene Expression Patterns of Calcium Channels and Related Signaling Pathways Discovered in Lymphomas"],"prefix":"10.3389","volume":"13","author":[{"given":"Shawna R.","family":"Stanwood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Steidl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred A.","family":"Jefferies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1158\/2159-8290.CD-19-0680","article-title":"Single-Cell Transcriptome Analysis Reveals Disease-Defining T-Cell Subsets in the Tumor Microenvironment of Classic Hodgkin Lymphoma","volume":"10","author":"Aoki","year":"2020","journal-title":"Cancer Discov."},{"key":"B2","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1177\/117693510700300004","article-title":"Germinal center B Cell-like (GCB) and Activated B Cell-like (ABC) Type of Diffuse Large B Cell Lymphoma (DLBCL): Analysis of Molecular Predictors, Signatures, Cell Cycle State and Patient Survival","volume":"3","author":"Blenk","year":"2007","journal-title":"Cancer Inform."},{"key":"B3","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41408-020-0322-5","article-title":"Combining Gene Expression Profiling and Machine Learning to Diagnose B-Cell Non-hodgkin Lymphoma","volume":"10","author":"Bob\u00e9e","year":"2020","journal-title":"Blood Cancer J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"7342","DOI":"10.1038\/sj.onc.1204926","article-title":"Transcriptional Regulation of Bcl-2 by Nuclear Factor Kappa B and its Significance in Prostate Cancer","volume":"20","author":"Catz","year":"2001","journal-title":"Oncogene"},{"key":"B5","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1200\/JCO.18.01583","article-title":"Double-hit Gene Expression Signature Defines a Distinct Subgroup of Germinal center B-cell-like Diffuse Large B-Cell Lymphoma","volume":"37","author":"Ennishi","year":"2019","journal-title":"J. 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