{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:25:26Z","timestamp":1786969526303,"version":"build-2736575974"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>The evolutionarily conserved Notch signaling pathway is a contact-dependent communication mechanism regulating cell fate, tissue patterning, and cellular metabolism. Beyond canonical NICD-RBPJ transcription, Notch engages in non-canonical crosstalk with networks like Wnt and NF-\u03baB. In tumor angiogenesis, the endothelial Foxc1\/2-DLL4-Notch1 axis coordinates tip\/stalk cell plasticity, while restricting glycolytic flux via PFKFB3 downregulation to promote vessel maturation. Consequently, pathway inhibition triggers non-productive hypersprouting and vascular collapse, whereas Notch activation strategies offer potential for therapeutic vessel normalization. Crucially, Notch acts as a driving oncogene in B-cell malignancies, promoting survival and chemoresistance. In mantle cell lymphoma (MCL), somatic mutations truncate the C-terminal PEST domain, preventing proteasomal degradation and inducing constitutive NICD hyperactivation\u2014defining an aggressive, microenvironment-sustained clinical subset. Similar NOTCH1\/2 aberrations drive clonal progression in marginal zone and MALT lymphomas, and indicate poor prognosis in Hepatitis C Virus-positive diffuse large B-cell lymphoma (DLBCL). Routine genomic screening for Notch alterations provides critical prognostic stratification, laying the basis for personalized, selective therapies in refractory hematological diseases.<\/jats:p>","DOI":"10.3389\/fonc.2026.1904760","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:33:44Z","timestamp":1786966424000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of notch signaling in tumor angiogenesis in hematological malignancies"],"prefix":"10.3389","volume":"16","author":[{"given":"Roberto","family":"Tamma","sequence":"first","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari Medical School","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Benagiano","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, 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