{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:21:39Z","timestamp":1747149699405,"version":"3.40.5"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent advances in treatment options for multiple myeloma (MM) have positive impact on patient survival. However, there is a short fall of rapid and reliable assays that can predict patient response to novel agents. The anti\u2010apoptotic proteins B\u2010cell lymphoma\u20102 (BCL\u20102) and myeloid cell leukaemia\u20101 (MCL\u20101), are necessary for MM survival, although most myelomas are more dependent on MCL\u20101. BCL\u20102 inhibition alone yields significant cytotoxicity in only a minority of cases, therefore targeting both proteins simultaneously, is a therapeutic option. Venetoclax and S63845 are BCL\u20102 and MCL\u20101 targeting BH3\u2010mimetics which have demonstrated apoptotic synergy in MM. We investigated whether a novel short\u2010term flow cytometric cytochrome c release assay could predict response to dual BH3\u2010mimetic targeting in MM cells. Six human myeloma cell lines (HMCL) and seven primary samples were treated with venetoclax and S63845 alone or in combination. The 4\u2010hour assay confirmed the drug combination was synergistic in all HMCL tested. Annexin\u2010V data at 48 hours corresponded with 4\u2010hour response verifying the assay as a predictor of drug sensitivity. All primary samples responded to the drug combination, including samples with 1q gain and t(4;14) translocation. Normal stem cells were unaffected by the drug combination. We have developed a novel assay with the potential to predict response to therapy in MM cells.<\/jats:p>","DOI":"10.1002\/jha2.133","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T22:34:58Z","timestamp":1605911698000},"page":"40-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A same\u2010day assay predicts apoptotic response to combined BCL\u20102 and MCL\u20101 BH3\u2010mimetic targeting in multiple myeloma cells"],"prefix":"10.1002","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1800-3694","authenticated-orcid":false,"given":"Martin","family":"Grundy","sequence":"first","affiliation":[{"name":"Blood Cancer and Stem Cells, Division of Cancer and Stem Cells School of Medicine University of Nottingham Biodiscovery Institute  Nottingham UK"},{"name":"Clinical Haematology Nottingham University Hospitals  Nottingham 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