{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:17:37Z","timestamp":1789017457641,"version":"build-2803163510"},"reference-count":62,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite major progress in mantle cell lymphoma (MCL) therapeutics, MCL remains a deadly disease with a median survival not exceeding four years. No single driver genetic lesion has been described to solely give rise to MCL. The hallmark translocation t(11;14)(q13;q32) requires additional genetic alterations for the malignant transformation. A short list of recurrently mutated genes including ATM, CCND1, UBR5, TP53, BIRC3, NOTCH1, NOTCH2, and TRAF2 recently emerged as contributors to the pathogenesis of MCL. Notably, NOTCH1 and NOTCH2 were found to be mutated in multiple B cell lymphomas, including 5\u201310% of MCL, with most of these mutations occurring within the PEST domain of the protein. The NOTCH genes play a critical role in the early and late phases of normal B cell differentiation. In MCL, mutations in the PEST domain stabilize NOTCH proteins, rendering them resistant to degradation, which subsequently results in the upregulation of genes involved in angiogenesis, cell cycle progression, and cell migration and adhesion. At the clinical level, mutated NOTCH genes are associated with aggressive features in MCL, such as the blastoid and pleomorphic variants, a shorter response to treatment, and inferior survival. In this article, we explore in detail the role of NOTCH signaling in MCL biology and the ongoing efforts toward targeted therapeutic interventions.<\/jats:p>","DOI":"10.3390\/ijms241210280","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:31:14Z","timestamp":1687138274000},"page":"10280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["NOTCH Signaling in Mantle Cell Lymphoma: Biological and Clinical Implications"],"prefix":"10.3390","volume":"24","author":[{"given":"Leigh","family":"Deshotels","sequence":"first","affiliation":[{"name":"Section of Hematology and Medical Oncology, Deming Department of Medicine, Tulane University, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9537-0578","authenticated-orcid":false,"given":"Firas","family":"Safa","sequence":"additional","affiliation":[{"name":"Service d\u2019h\u00e9matologie, Centre Hospitalier du Mans, 72037 Le Mans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakhle","family":"Saba","sequence":"additional","affiliation":[{"name":"Section of Hematology and Medical Oncology, Deming Department of Medicine, Tulane University, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1182\/blood-2018-03-791392","article-title":"Update on mantle cell lymphoma","volume":"132","author":"Maddocks","year":"2018","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/hon.2860","article-title":"Mantle cell lymphoma-Advances in molecular biology, prognostication and treatment approaches","volume":"39","author":"Silkenstedt","year":"2021","journal-title":"Hematol. 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