{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:34:00Z","timestamp":1791182040355,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T00:00:00Z","timestamp":1379548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100003943","name":"The Mastocytosis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003943","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["#P21173-B13"],"award-info":[{"award-number":["#P21173-B13"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["SFB-F4704-B20"],"award-info":[{"award-number":["SFB-F4704-B20"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Advanced SM is an incurable neoplasm with short survival time. So far, no effective therapy is available for these patients. We and others have shown recently that neoplastic MC in ASM and MCL express antiapoptotic Mcl-1, Bcl-2, and Bcl-xL. In this study, we examined the effects of the pan-Bcl-2 family blocker obatoclax (GX015-070) on primary neoplastic MC, the human MC leukemia cell line HMC-1, and the canine mastocytoma cell line C2. Obatoclax was found to inhibit proliferation in primary human neoplastic MC (IC50: 0.057 \u03bcM), in HMC-1.2 cells expressing KIT D816V (IC50: 0.72 \u03bcM), and in HMC-1.1 cells lacking KIT D816V (IC50: 0.09 \u03bcM), as well as in C2 cells (IC50: 0.74 \u03bcM). The growth-inhibitory effects of obatoclax in HMC-1 cells were accompanied by an increase in expression of Puma, Noxa, and Bim mRNA, as well as by apoptosis, as evidenced by microscopy, TUNEL assay, and caspase cleavage. Viral-mediated overexpression of Mcl-1, Bcl-xL, or Bcl-2 in HMC-1 cells was found to introduce partial resistance against apoptosis-inducing effects of obatoclax. We were also able to show that obatoclax synergizes with several other antineoplastic drugs, including dasatinib, midostaurin, and bortezomib, in producing apoptosis and\/or growth arrest in neoplastic MC. Together, obatoclax exerts major growth-inhibitory effects on neoplastic MC and potentiates the antineoplastic activity of other targeted drugs. Whether these drug effects can be translated to application in patients with advanced SM remains to be determined.<\/jats:p>","DOI":"10.1189\/jlb.1112609","type":"journal-article","created":{"date-parts":[[2013,9,20]],"date-time":"2013-09-20T09:22:14Z","timestamp":1379668934000},"page":"95-104","source":"Crossref","is-referenced-by-count":29,"title":["The pan-Bcl-2 blocker obatoclax promotes the expression of Puma, Noxa, and Bim mRNA and induces apoptosis in neoplastic mast cells"],"prefix":"10.1093","volume":"95","author":[{"given":"Barbara","family":"Peter","sequence":"first","affiliation":[{"name":"Ludwig-Boltzmann Cluster Oncology, Medical University of Vienna , Austria"},{"name":"Department for Companion Animals and Horses, Clinic for Internal Medicine and Infectious Diseases, University of Veterinary Medicine , Vienna, Austria"},{"name":"Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna , 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Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Schuch","sequence":"additional","affiliation":[{"name":"Institutes of Immunology, Medical University of Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Stefanzl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Eisenwort","sequence":"additional","affiliation":[{"name":"Ludwig-Boltzmann Cluster Oncology, Medical University of Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline V","family":"Gleixner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Hoermann","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Mayerhofer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Vienna , Austria"},{"name":"Hanusch Hospital, Department of Laboratory Medicine , Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kundi","sequence":"additional","affiliation":[{"name":"Environmental Health, Center for Public Health, Medical University of Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Medical University of Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang R","family":"Sperr","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried F","family":"Pickl","sequence":"additional","affiliation":[{"name":"Institutes of Immunology, Medical University of Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Willmann","sequence":"additional","affiliation":[{"name":"Department for Companion Animals and Horses, Clinic for Internal Medicine and Infectious Diseases, University of Veterinary Medicine , Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Valent","sequence":"additional","affiliation":[{"name":"Ludwig-Boltzmann Cluster Oncology, Medical University of Vienna , Austria"},{"name":"Department 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