{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:32:11Z","timestamp":1791325931823,"version":"4.3.1"},"reference-count":59,"publisher":"Impact Journals, LLC","issue":"29","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncotarget"],"published-print":{"date-parts":[[2015,9,29]]},"DOI":"10.18632\/oncotarget.4489","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T17:43:03Z","timestamp":1443548583000},"page":"27388-27402","source":"Crossref","is-referenced-by-count":65,"title":["A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2"],"prefix":"10.18632","volume":"6","author":[{"given":"Andrew R.","family":"Lavik","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Jin","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USA"},{"name":"Department of Medicine, MetroHealth Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuvraj","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA"},{"name":"Case Comprehensive Cancer Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S.","family":"McColl","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pink","sequence":"additional","affiliation":[{"name":"Case Comprehensive Cancer Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic J.","family":"Reu","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA"},{"name":"Case Comprehensive Cancer Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigemi","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USA"},{"name":"Case Comprehensive Cancer Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clark W.","family":"Distelhorst","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USA"},{"name":"Case Comprehensive Cancer Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7892","published-online":{"date-parts":[[2015,7,11]]},"reference":[{"key":"1","doi-asserted-by":"crossref","first-page":"6398","DOI":"10.1038\/onc.2008.307","article-title":"Bcl-2 family proteins and cancer","volume":"27","author":"Reed","year":"2008","journal-title":"Oncogene"},{"key":"2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Weinberg","year":"2011","journal-title":"Cell"},{"key":"3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrm2308","article-title":"The Bcl-2 protein family: opposing activities that mediate cell death","volume":"9","author":"Strasser","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.molcel.2010.01.025","article-title":"The BCL-2 family reunion","volume":"37","author":"Green","year":"2010","journal-title":"Mol Cell"},{"key":"5","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1158\/0008-5472.CAN-07-5836","article-title":"ABT-263: A potent and orally bioavailable Bcl-2 family inhibitor","volume":"68","author":"Fesik","year":"2008","journal-title":"Cancer Res"},{"key":"6","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nm.3048","article-title":"ABT-9, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets","volume":"19","author":"Lam","year":"2013","journal-title":"Nat Med"},{"key":"7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrc2297","article-title":"Diagnosing and exploiting cancer\u2019s addiction to blocks in apoptosis","volume":"8","author":"Letai","year":"2008","journal-title":"Nat Rev Cancer"},{"key":"8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ccr.2013.01.018","article-title":"ABT-199: taking dead aim at BCL-2","volume":"23","author":"Letai","year":"2013","journal-title":"Cancer Cell"},{"key":"9","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1182\/blood-2013-01-475855","article-title":"ABT-199, a new Bcl-2-specific BH3 mimetic, hasefficacy against aggressive Myc-driven mouse lymphomas without provoking thrombocytopenia","volume":"121","author":"Cory","year":"2013","journal-title":"Blood"},{"key":"10","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1016\/j.bbamcr.2014.03.008","article-title":"Bcl-2 regulation of the inositol 1,4,5-trisphosphate receptor and calcium signaling in normal and malignant lymphocytes: Potential new target for cancer treatment","volume":"1843","author":"Distelhorst","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"11","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1016\/j.bbamcr.2014.04.017","article-title":"A dual role for the anti-apoptotic Bcl-2 protein in cancer: mitochondria versus endoplasmic reticulum","volume":"1843","author":"Bultynck","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"12","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1073\/pnas.1323098111","article-title":"Feedback regulation mediated by Bcl-2 and DARPP-32 regulates inositol 1,4,5-trisphosphate receptor phosphorylation and promotes cell survival","volume":"111","author":"Distelhorst","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"13","doi-asserted-by":"crossref","first-page":"14397","DOI":"10.1073\/pnas.0907555106","article-title":"The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IPreceptor","volume":"106","author":"Distelhorst","year":"2009","journal-title":"Proc Natl Acad Sci"},{"key":"14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/cdd.2011.97","article-title":"Selective regulation of IP(3)-receptor-mediated Ca(2+) signaling and apoptosis by the BH4 domain of Bcl-2 versus Bcl-Xl","volume":"19","author":"Bultynck","year":"2012","journal-title":"Cell Death Differ"},{"key":"15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.molcel.2008.06.014","article-title":"Targeting Bcl-2-IPreceptor interaction to reverse Bcl-2\u2032s inhibition of apoptotic calcium signals","volume":"31","author":"Distelhorst","year":"2008","journal-title":"Mol Cell"},{"key":"16","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1182\/blood-2010-09-307405","article-title":"Induction of Ca-driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2-IPreceptor interaction","volume":"117","author":"Distelhorst","year":"2011","journal-title":"Blood"},{"key":"17","doi-asserted-by":"crossref","first-page":"e632","DOI":"10.1038\/cddis.2013.140","article-title":"IP3R2 levels dictate the apoptotic sensitivity of diffuse large B-cell lymphoma cells to an IPR-derived peptide targeting the BH4 domain of Bcl-2","volume":"4","author":"Bultynck","year":"2013","journal-title":"Cell Death Dis"},{"key":"18","doi-asserted-by":"crossref","first-page":"8076","DOI":"10.1038\/sj.onc.1208949","article-title":"Melphalan-induced apoptosis in multiple myeloma cells is associated with a cleavage of Mcl-1 and Bim and a decrease in the Mcl-1\/\/Bim complex","volume":"24","author":"Amiot","year":"2005","journal-title":"Oncogene"},{"key":"19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/cgt.2012.84","article-title":"A review of the role of Puma, Noxa and Bim in the tumorigenesis, therapy and drug resistance of chronic lymphocytic leukemia","volume":"20","author":"Xu","year":"2013","journal-title":"Cancer Gene Ther"},{"key":"20","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1172\/JCI28281","article-title":"Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737","volume":"117","author":"Letai","year":"2007","journal-title":"J Clin Invest"},{"key":"21","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.4049\/jimmunol.176.4.2299","article-title":"Thymocyte negative selection is mediated by protein kinase C- and Ca-dependent transcriptional induction of Bim of cell death","volume":"176","author":"Crabtree","year":"2006","journal-title":"J Immunol"},{"key":"22","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/0165-4608(93)90132-6","article-title":"A unique EBV-negative low-grade lymphoma line (WSU-FSCCL) exhibiting both t(14, 18) and t(8;11)","volume":"70","author":"Al-Katib","year":"1993","journal-title":"Cancer Genetics and Cytogenetics"},{"key":"23","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/leu.2013.216","article-title":"The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11, 14) multiple myeloma","volume":"28","author":"Amiot","year":"2014","journal-title":"Leukemia"},{"key":"24","doi-asserted-by":"crossref","first-page":"574","DOI":"10.3324\/haematol.2010.033456","article-title":"A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines","volume":"96","author":"Pellat-Deceunynck","year":"2011","journal-title":"Haematologica"},{"key":"25","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1126\/science.286.5445.1735","article-title":"Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity","volume":"286","author":"Strasser","year":"1999","journal-title":"Science"},{"key":"26","doi-asserted-by":"crossref","first-page":"23861","DOI":"10.1074\/jbc.M301843200","article-title":"Microarray analysis uncovers the induction of the proapoptotic BH3-only protein Bim in multiple models of glucocorticoid-induced apoptosis","volume":"278","author":"Distelhorst","year":"2003","journal-title":"J Biol Chem"},{"key":"27","doi-asserted-by":"crossref","first-page":"20858","DOI":"10.1074\/jbc.M310643200","article-title":"The pro-apoptotic protein Bim is a convergence point for cAMP\/protein kinase A- and glucocorticoid-promoted apoptosis in lymphoid cells","volume":"279","author":"Insel","year":"2004","journal-title":"J Biol Chem"},{"key":"28","doi-asserted-by":"crossref","first-page":"4131","DOI":"10.1182\/blood-2005-04-1595","article-title":"BH3-only proteins Puma and Bim are rate-limiting for gamma-radiation- and glucocorticoid-induced apoptosis of lymphoid cells","volume":"106","author":"Villunger","year":"2005","journal-title":"Blood"},{"key":"29","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1038\/onc.2014.181","article-title":"BTK inhibitors in chronic lymphocytic leukemia: a glimpse to the future","volume":"34","author":"Eldering","year":"2015","journal-title":"Oncogene"},{"key":"30","doi-asserted-by":"crossref","first-page":"6287","DOI":"10.1182\/blood-2011-01-328484","article-title":"Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765","volume":"117","author":"Byrd","year":"2011","journal-title":"Blood"},{"key":"31","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1182\/blood-2011-11-390989","article-title":"The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia","volume":"119","author":"Spaargaren","year":"2012","journal-title":"Blood"},{"key":"32","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/leu.2013.358","article-title":"BTK inhibition targetsCLL proliferation through its effects on B-cell receptor signaling activity","volume":"28","author":"Wang","year":"2014","journal-title":"Leukemia"},{"key":"33","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s40265-014-0178-8","article-title":"Ibrutinib: First Global Approval","volume":"74","author":"Sanford","year":"2014","journal-title":"Drugs"},{"key":"34","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1158\/0008-5472.CAN-14-2362","article-title":"Bruton Tyrosine Kinase Is a Therapeutic Target in Stem-like Cells from Multiple Myeloma","volume":"75","author":"Zhan","year":"2015","journal-title":"Cancer Research"},{"key":"35","first-page":"2012","article-title":"Bruton\u2019s tyrosine kinase: oncotarget in myeloma","volume":"3","author":"Anderson","year":"2012","journal-title":"Oncotarget"},{"key":"36","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/bjh.12974","article-title":"Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells","volume":"166","author":"Wang","year":"2014","journal-title":"British Journal of Haematology"},{"key":"37","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1475-2867-14-32","article-title":"Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment","volume":"14","author":"Zhu","year":"2014","journal-title":"Cancer Cell International"},{"key":"38","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1056\/NEJMoa1400029","article-title":"Resistance Mechanisms for the Bruton\u2019s Tyrosine Kinase Inhibitor Ibrutinib","volume":"370","author":"Lozanski","year":"2014","journal-title":"New England Journal of Medicine"},{"key":"39","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1056\/NEJMc1402716","article-title":"Ibrutinib Resistance in Chronic Lymphocytic Leukemia","volume":"370","author":"Wang","year":"2014","journal-title":"New England Journal of Medicine"},{"key":"40","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1182\/blood-2015-02-626846","article-title":"Hypermorphic mutation of phospholipase C, gamma 2 acquired in ibrutinib resistant CLL confers BTK independency upon BCR activation","volume":"126","author":"Byrd","year":"2015","journal-title":"Blood"},{"key":"41","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1182\/blood.V79.2.495.495","article-title":"Expression of the bcl-2 gene in human multiple myeloma cell lines and normal plasma cells","volume":"79","author":"Nilsson","year":"1992","journal-title":"Blood"},{"key":"42","doi-asserted-by":"crossref","first-page":"13075","DOI":"10.1073\/pnas.1004594107","article-title":"The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy","volume":"107","author":"Buggy","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"43","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1200\/JCO.2012.42.7906","article-title":"Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed\/refractory B-cell malignancies","volume":"31","author":"Fowler","year":"2013","journal-title":"J Clin Oncol"},{"key":"44","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1182\/blood-2013-06-507947","article-title":"Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes","volume":"122","author":"Flynn","year":"2013","journal-title":"Blood"},{"key":"45","doi-asserted-by":"crossref","first-page":"E966","DOI":"10.1073\/pnas.1500712112","article-title":"Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK","volume":"112","author":"Levy","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"46","first-page":"2013","article-title":"Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms","volume":"4","author":"Chang","year":"2013","journal-title":"Oncotarget"},{"key":"47","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/S0140-6736(14)60493-1","article-title":"Multiple myeloma","volume":"385","author":"Bornh\u00e4user","year":"2015","journal-title":"The Lancet"},{"key":"48","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1038\/leu.2014.91","article-title":"How we manage follicular lymphoma","volume":"28","author":"Cheson","year":"2014","journal-title":"Leukemia"},{"key":"49","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1038\/sj.onc.1210028","article-title":"A novel Bcl-2\/Bcl-X(L)\/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma","volume":"26","author":"Anderson","year":"2007","journal-title":"Oncogene"},{"key":"50","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1038\/sj.leu.2404719","article-title":"ABT-737, an inhibitor of Bcl-2 family proteins, is a potent inducer of apoptosis in multiple myeloma cells","volume":"21","author":"Kumar","year":"2007","journal-title":"Leukemia"},{"key":"51","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1158\/1078-0432.CCR-06-1526","article-title":"The Bcl-2 family protein inhibitor, ABT-737, has substantial antimyeloma activity and shows synergistic effect with dexamethasone and melphalan","volume":"13","author":"Wen","year":"2007","journal-title":"Clin Cancer Res"},{"key":"52","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1182\/blood-2010-11-317438","article-title":"ABT-737 is highly effective against molecular subgroups of multiple myeloma","volume":"118","author":"Amiot","year":"2011","journal-title":"Blood"},{"key":"53","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1083\/jcb.200309146","article-title":"Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER","volume":"166","author":"Distelhorst","year":"2004","journal-title":"J Cell Biol"},{"key":"54","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrc2374","article-title":"Casignalling checkpoints in cancer: remodelling Cafor cancer cell proliferation and survival","volume":"8","author":"Cook","year":"2008","journal-title":"Nat Rev Cancer"},{"key":"55","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nrc3105","article-title":"Calcium in tumour metastasis: new roles for known actors","volume":"11","author":"Shuba","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"56","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrc2171","article-title":"Calcium and cancer: targeting Catransport","volume":"7","author":"Roberts-Thomson","year":"2007","journal-title":"Nat Rev Cancer"},{"key":"57","doi-asserted-by":"crossref","first-page":"5299","DOI":"10.18632\/oncotarget.3024","article-title":"High expression of inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) as a novel biomarker for worse prognosis in cytogenetically normal acute myeloid leukemia","volume":"6","author":"Wang","year":"2015","journal-title":"Oncotarget"},{"key":"58","doi-asserted-by":"crossref","first-page":"e309","DOI":"10.1038\/cddis.2012.43","article-title":"Inhibition of Bax protects neuronal cells from oligomeric A \u03b2 neurotoxicity","volume":"3","author":"Lee","year":"2012","journal-title":"Cell Death Dis"},{"key":"59","doi-asserted-by":"crossref","first-page":"27863","DOI":"10.1074\/jbc.M112.384685","article-title":"Acidosis Promotes Bcl-2 Family Mediated Evasion of Apoptosis: Involvement of Acid-Sensing G Protein-Coupled Receptor GPR65 Signaling to MEK\/ERK","volume":"287","author":"Distelhorst","year":"2012","journal-title":"J Biol Chem"}],"container-title":["Oncotarget"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.4489","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T15:56:58Z","timestamp":1589385418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.4489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,11]]},"references-count":59,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2015,9,29]]}},"alternative-id":["4489","26317541"],"URL":"https:\/\/doi.org\/10.18632\/oncotarget.4489","relation":{},"ISSN":["1949-2553"],"issn-type":[{"value":"1949-2553","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,11]]}}}