{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:54:42Z","timestamp":1789012482998,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":34,"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":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mantle cell lymphoma (MCL) is an aggressive and largely incurable subtype of non\u2010Hodgkin's lymphoma. Venetoclax has demonstrated efficacy in MCL patients with relapsed or refractory disease, however response is variable and less durable than CLL. This may be the result of co\u2010expression of other anti\u2010apoptotic proteins such as MCL\u20101, which is associated with both intrinsic and acquired resistance to venetoclax in B\u2010cell malignancies. One strategy for neutralizing MCL\u20101 and other short\u2010lived survival factors is to inhibit CDK9, which plays a key role in transcription. Here, we report the response of MCL cell lines and primary patient samples to the combination of venetoclax and novel CDK9 inhibitors. Primary samples represented de novo patients and relapsed disease, including relapse after ibrutinib failure. Despite the diverse responses to each single agent, possibly due to variable expression of the BCL\u20102 family members, venetoclax plus CDK9 inhibitors synergistically induced apoptosis in MCL cells. The synergistic effect was also confirmed via venetoclax plus a direct MCL\u20101 inhibitor. Murine xenograft studies demonstrated potent in vivo efficacy of venetoclax plus CDK9 inhibitor that was superior to each agent alone. Together, this study supports clinical investigation of this combination in MCL, including in patients who have progressed on ibrutinib.<\/jats:p>","DOI":"10.1002\/jha2.48","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T19:39:13Z","timestamp":1596569953000},"page":"161-169","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of cyclin\u2010dependent kinase 9 synergistically enhances venetoclax activity in mantle cell lymphoma"],"prefix":"10.1002","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8761-3170","authenticated-orcid":false,"given":"Xiaoxian","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Robert J. Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4987-728X","authenticated-orcid":false,"given":"Juraj","family":"Bodo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Robert J. Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Robert J. Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Durkin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Robert J. Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Souers","sequence":"additional","affiliation":[{"name":"Oncology Discovery AbbVie Inc.  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren C.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Oncology Discovery AbbVie Inc.  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Hsi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Robert J. 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