{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:15:34Z","timestamp":1788372934982,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"publisher","award":["20614"],"award-info":[{"award-number":["20614"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"publisher","award":["25739"],"award-info":[{"award-number":["25739"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"publisher","award":["24365"],"award-info":[{"award-number":["24365"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"publisher","award":["R21CA194679"],"award-info":[{"award-number":["R21CA194679"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"publisher","award":["Current research IRCCS"],"award-info":[{"award-number":["Current research IRCCS"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"publisher","award":["Linea 2B-2017"],"award-info":[{"award-number":["Linea 2B-2017"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"publisher","award":["R37CA252040"],"award-info":[{"award-number":["R37CA252040"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NCI Provocative Questions award","award":["20614"],"award-info":[{"award-number":["20614"]}]},{"name":"NCI Provocative Questions award","award":["25739"],"award-info":[{"award-number":["25739"]}]},{"name":"NCI Provocative Questions award","award":["24365"],"award-info":[{"award-number":["24365"]}]},{"name":"NCI Provocative Questions award","award":["R21CA194679"],"award-info":[{"award-number":["R21CA194679"]}]},{"name":"NCI Provocative Questions award","award":["Current research IRCCS"],"award-info":[{"award-number":["Current research IRCCS"]}]},{"name":"NCI Provocative Questions award","award":["Linea 2B-2017"],"award-info":[{"award-number":["Linea 2B-2017"]}]},{"name":"NCI Provocative Questions award","award":["R37CA252040"],"award-info":[{"award-number":["R37CA252040"]}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["20614"],"award-info":[{"award-number":["20614"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["25739"],"award-info":[{"award-number":["25739"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["24365"],"award-info":[{"award-number":["24365"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["R21CA194679"],"award-info":[{"award-number":["R21CA194679"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["Current research IRCCS"],"award-info":[{"award-number":["Current research IRCCS"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["Linea 2B-2017"],"award-info":[{"award-number":["Linea 2B-2017"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["R37CA252040"],"award-info":[{"award-number":["R37CA252040"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","award":["20614"],"award-info":[{"award-number":["20614"]}],"id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","award":["25739"],"award-info":[{"award-number":["25739"]}],"id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","award":["24365"],"award-info":[{"award-number":["24365"]}],"id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","award":["R21CA194679"],"award-info":[{"award-number":["R21CA194679"]}],"id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","award":["Current research IRCCS"],"award-info":[{"award-number":["Current research IRCCS"]}],"id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","award":["Linea 2B-2017"],"award-info":[{"award-number":["Linea 2B-2017"]}],"id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","award":["R37CA252040"],"award-info":[{"award-number":["R37CA252040"]}],"id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Leukemia &amp; Lymphoma Society and the National Cancer Institute","award":["20614"],"award-info":[{"award-number":["20614"]}]},{"name":"The Leukemia &amp; Lymphoma Society and the National Cancer Institute","award":["25739"],"award-info":[{"award-number":["25739"]}]},{"name":"The Leukemia &amp; Lymphoma Society and the National Cancer Institute","award":["24365"],"award-info":[{"award-number":["24365"]}]},{"name":"The Leukemia &amp; Lymphoma Society and the National Cancer Institute","award":["R21CA194679"],"award-info":[{"award-number":["R21CA194679"]}]},{"name":"The Leukemia &amp; Lymphoma Society and the National Cancer Institute","award":["Current research IRCCS"],"award-info":[{"award-number":["Current research IRCCS"]}]},{"name":"The Leukemia &amp; Lymphoma Society and the National Cancer Institute","award":["Linea 2B-2017"],"award-info":[{"award-number":["Linea 2B-2017"]}]},{"name":"The Leukemia &amp; Lymphoma Society and the National Cancer Institute","award":["R37CA252040"],"award-info":[{"award-number":["R37CA252040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The NOTCH ligands JAG1 and JAG2 have been correlated in vitro with multiple myeloma (MM) cell proliferation, drug resistance, self-renewal and a pathological crosstalk with the tumor microenvironment resulting in angiogenesis and osteoclastogenesis. These findings suggest that a therapeutic approach targeting JAG ligands might be helpful for the care of MM patients and lead us to explore the role of JAG1 and JAG2 in a MM in vivo model and primary patient samples. JAG1 and JAG2 protein expression represents a common feature in MM cell lines; therefore, we assessed their function through JAG1\/2 conditional silencing in a MM xenograft model. We observed that JAG1 and JAG2 showed potential as therapeutic targets in MM, as their silencing resulted in a reduction in the tumor burden. Moreover, JAG1 and JAG2 protein expression in MM patients was positively correlated with the presence of MM cells in patients\u2019 bone marrow biopsies. Finally, taking advantage of the Multiple Myeloma Research Foundation (MMRF) CoMMpass global dataset, we showed that JAG2 gene expression level was a predictive biomarker associated with patients\u2019 overall survival and progression-free survival, independently from other main molecular or clinical features. Overall, these results strengthened the rationale for the development of a JAG1\/2-tailored approach and the use of JAG2 as a predictive biomarker in MM.<\/jats:p>","DOI":"10.3390\/ijms241914558","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T03:45:23Z","timestamp":1695699923000},"page":"14558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Potential of JAG Ligands as Therapeutic Targets and Predictive Biomarkers in Multiple Myeloma"],"prefix":"10.3390","volume":"24","author":[{"given":"Natalia","family":"Platonova","sequence":"first","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Lazzari","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Division of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, La Jolla, CA 92093, USA"},{"name":"UC San Diego Sanford, Stem Cell Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2252-1424","authenticated-orcid":false,"given":"Michela","family":"Colombo","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Falleni","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Unit of Pathology A.O. San Paolo, Via A. Di Rudin\u00ec 8, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-2665","authenticated-orcid":false,"given":"Delfina","family":"Tosi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Unit of Pathology A.O. San Paolo, Via A. Di Rudin\u00ec 8, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Giannandrea","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0289-404X","authenticated-orcid":false,"given":"Valentina","family":"Citro","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9044-6767","authenticated-orcid":false,"given":"Lavinia","family":"Casati","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4824-3445","authenticated-orcid":false,"given":"Domenica","family":"Ronchetti","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-5139","authenticated-orcid":false,"given":"Niccol\u00f2","family":"Bolli","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"},{"name":"Hematology, Fondazione C\u00e0 Granda IRCCS Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Neri","sequence":"additional","affiliation":[{"name":"Scientific Directorate, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Torricelli","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie A.","family":"Crews","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona H. M.","family":"Jamieson","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, La Jolla, CA 92093, USA"},{"name":"UC San Diego Sanford, Stem Cell Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1078-1704","authenticated-orcid":false,"given":"Raffaella","family":"Chiaramonte","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s11899-020-00570-9","article-title":"Supportive Care in Multiple Myeloma","volume":"15","author":"Guzdar","year":"2020","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1080\/14789450.2020.1845654","article-title":"Multiomic analysis of cytokines in immuno-oncology","volume":"17","author":"Jurisic","year":"2020","journal-title":"Expert Rev. Proteom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cyto.2019.02.001","article-title":"The role of cytokines in the regulation of NK cells in the tumor environment","volume":"117","author":"Larsen","year":"2019","journal-title":"Cytokine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s11914-017-0399-3","article-title":"Bone Marrow Stroma and Vascular Contributions to Myeloma Bone Homing","volume":"15","author":"Moschetta","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1677\/JOE-07-0242","article-title":"Cell and molecular biology of Notch","volume":"194","author":"Fiuza","year":"2007","journal-title":"J. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.15252\/embr.201438842","article-title":"Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human","volume":"15","author":"Kushwah","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1146\/annurev-pathol-052016-100127","article-title":"The Varied Roles of Notch in Cancer","volume":"12","author":"Aster","year":"2017","journal-title":"Annu. Rev. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1182\/blood-2004-02-0704","article-title":"Notch signaling: A key to the pathogenesis of multiple myeloma?","volume":"103","author":"Milner","year":"2004","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.1182\/blood-2003-07-2254","article-title":"Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells","volume":"103","author":"Jundt","year":"2004","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s12185-011-0948-y","article-title":"The use of molecular-based risk stratification and pharmacogenomics for outcome prediction and personalized therapeutic management of multiple myeloma","volume":"94","author":"Johnson","year":"2011","journal-title":"Int. J. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1182\/blood-2004-01-0037","article-title":"Advances in biology of multiple myeloma: Clinical applications","volume":"104","author":"Hideshima","year":"2004","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1016\/j.humpath.2010.05.002","article-title":"Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance","volume":"41","author":"Dominis","year":"2010","journal-title":"Hum. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"56013","DOI":"10.18632\/oncotarget.10820","article-title":"Multiple myeloma-derived Jagged ligands increases autocrine and paracrine interleukin-6 expression in bone marrow niche","volume":"7","author":"Colombo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1182\/blood-2003-12-4114","article-title":"Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines","volume":"104","author":"Houde","year":"2004","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/S0002-9440(10)62491-1","article-title":"Skeletrophin, a novel ubiquitin ligase to the intracellular region of Jagged-2, is aberrantly expressed in multiple myeloma","volume":"166","author":"Takeuchi","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4380","DOI":"10.1158\/0008-5472.CAN-08-3467","article-title":"Loss of the SMRT\/NCoR2 corepressor correlates with JAG2 overexpression in multiple myeloma","volume":"69","author":"Ghoshal","year":"2009","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/leu.2013.27","article-title":"Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4\/SDF-1","volume":"27","author":"Mirandola","year":"2013","journal-title":"Leukemia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.3324\/haematol.2019.221077","article-title":"Multiple myeloma exploits Jagged1 and Jagged2 to promote intrinsic and bone marrow-dependent drug resistance","volume":"105","author":"Colombo","year":"2020","journal-title":"Haematologica"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41408-017-0001-3","article-title":"Jagged1-induced Notch activation contributes to the acquisition of bortezomib resistance in myeloma cells","volume":"7","author":"Muguruma","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1182\/blood-2003-07-2340","article-title":"Involvement of Notch-1 signaling in bone marrow stroma-mediated de novo drug resistance of myeloma and other malignant lymphoid cell lines","volume":"103","author":"Nefedova","year":"2004","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Palano, M.T., Giannandrea, D., Platonova, N., Gaudenzi, G., Falleni, M., Tosi, D., Lesma, E., Citro, V., Colombo, M., and Saltarella, I. (2020). Jagged Ligands Enhance the Pro-Angiogenic Activity of Multiple Myeloma Cells. Cancers, 12.","DOI":"10.3390\/cancers12092600"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.neo.2018.10.011","article-title":"Homotypic and Heterotypic Activation of the Notch Pathway in Multiple Myeloma-Enhanced Angiogenesis: A Novel Therapeutic Target?","volume":"21","author":"Saltarella","year":"2019","journal-title":"Neoplasia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.3324\/haematol.2021.279716","article-title":"Extracellular vesicles mediate the communication between multiple myeloma and bone marrow microenvironment in a NOTCH dependent way","volume":"107","author":"Giannandrea","year":"2022","journal-title":"Haematologica"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100785","DOI":"10.1016\/j.neo.2022.100785","article-title":"Notch3 signaling between myeloma cells and osteocytes in the tumor niche promotes tumor growth and bone destruction","volume":"28","author":"Sabol","year":"2022","journal-title":"Neoplasia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R45","DOI":"10.1186\/ar3758","article-title":"Differential regulation of osteoclastogenesis by Notch2\/Delta-like 1 and Notch1\/Jagged1 axes","volume":"14","author":"Sekine","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1158\/0008-5472.CAN-15-1703","article-title":"Bidirectional Notch Signaling and Osteocyte-Derived Factors in the Bone Marrow Microenvironment Promote Tumor Cell Proliferation and Bone Destruction in Multiple Myeloma","volume":"76","author":"Anderson","year":"2016","journal-title":"Cancer Res."},{"key":"ref_27","first-page":"20","article-title":"The multifunctional role of Notch signaling in multiple myeloma","volume":"7","author":"Sabol","year":"2021","journal-title":"J. Cancer Metastasis Treat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.bcmd.2012.01.006","article-title":"Critical role of the NOTCH ligand JAG2 in self-renewal of myeloma cells","volume":"48","author":"Chiron","year":"2012","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.neo.2014.10.004","article-title":"Notch3\/Jagged1 circuitry reinforces notch signaling and sustains T-ALL","volume":"16","author":"Pelullo","year":"2014","journal-title":"Neoplasia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1038\/s41467-017-01890-w","article-title":"Alu-dependent RNA editing of GLI1 promotes malignant regeneration in multiple myeloma","volume":"8","author":"Lazzari","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1158\/2159-8290.CD-14-1501","article-title":"Blockade of specific NOTCH ligands: A new promising approach in cancer therapy","volume":"5","author":"Briot","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12876","DOI":"10.1074\/jbc.M311652200","article-title":"Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation","volume":"279","author":"Wong","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/toxsci\/kfh254","article-title":"Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation","volume":"82","author":"Milano","year":"2004","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1158\/2159-8290.CD-14-0650","article-title":"NOTCH decoys that selectively block DLL\/NOTCH or JAG\/NOTCH disrupt angiogenesis by unique mechanisms to inhibit tumor growth","volume":"5","author":"Kangsamaksin","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.ccell.2017.11.002","article-title":"Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy","volume":"32","author":"Zheng","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.1158\/0008-5472.CAN-17-0357","article-title":"Anti-Jagged Immunotherapy Inhibits MDSCs and Overcomes Tumor-Induced Tolerance","volume":"77","author":"Sierra","year":"2017","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5674","DOI":"10.1158\/1078-0432.CCR-11-0432","article-title":"Targeting the notch ligand JAGGED1 in both tumor cells and stroma in ovarian cancer","volume":"17","author":"Steg","year":"2011","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1158\/1535-7163.MCT-18-1176","article-title":"Development of Therapeutic Anti-JAGGED1 Antibodies for Cancer Therapy","volume":"18","author":"Masiero","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Platonova, N., Parravicini, C., Sensi, C., Paoli, A., Colombo, M., Neri, A., Eberini, I., and Chiaramonte, R. (2017). Identification of small molecules uncoupling the Notch::Jagged interaction through an integrated high-throughput screening. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182640"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1002\/gcc.22264","article-title":"PI3K\/AKT signaling inhibits NOTCH1 lysosome-mediated degradation","volume":"54","author":"Platonova","year":"2015","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1385\/MO:19:3:133","article-title":"Correlation of sera TNF-alpha with percentage of bone marrow plasma cells, LDH, beta2-microglobulin, and clinical stage in multiple myeloma","volume":"19","author":"Jurisic","year":"2002","journal-title":"Med. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1182\/blood.V128.22.374.374","article-title":"A Comparison of Clinical FISH and Sequencing Based FISH Estimates in Multiple Myeloma: An Mmrf Commpass Analysis","volume":"128","author":"Miller","year":"2016","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"921","DOI":"10.3324\/haematol.2021.278342","article-title":"DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome","volume":"107","author":"Todoerti","year":"2022","journal-title":"Haematologica"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14558\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:58:24Z","timestamp":1760129904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":43,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms241914558"],"URL":"https:\/\/doi.org\/10.3390\/ijms241914558","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,26]]}}}