{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:13:58Z","timestamp":1784553238266,"version":"3.55.0"},"reference-count":119,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T00:00:00Z","timestamp":1683936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Relapsed and\/or refractory (R\/R) acute myeloid leukemia (AML) is hallmarked by dramatic prognosis. Treatment remains challenging, with allogeneic hematopoietic stem cell transplantation (HSCT) as the only curative option. The BCL-2 inhibitor venetoclax (VEN) has proven to be a promising therapy for AML and is currently the standard of care in combination with hypomethylating agents (HMAs) for newly diagnosed AML patients ineligible for induction chemotherapy. Given its satisfactory safety profile, VEN-based combinations are increasingly being investigated as a part of the therapeutic strategy for R\/R AML. The current paper aims to provide a comprehensive review of the main evidence regarding VEN in the setting of R\/R AML, with a specific focus on combinational strategies, including HMAs and cytotoxic chemotherapy, as well as different clinical settings, especially in view of the crucial role of HSCT. A discussion of what is known about drug resistance mechanisms and future combinational strategies is also provided. Overall, VEN-based regimes (mainly VEN + HMA) have provided unprecedented salvage treatment opportunities in patients with R\/R AML, with low extra-hematological toxicity. On the other hand, the issue of overcoming resistance is one of the most important fields to be addressed in upcoming clinical research.<\/jats:p>","DOI":"10.3390\/bioengineering10050591","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T08:33:01Z","timestamp":1684139581000},"page":"591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Role of Venetoclax in Relapsed\/Refractory Acute Myeloid Leukemia: Past, Present, and Future Directions"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9653-4976","authenticated-orcid":false,"given":"Matteo","family":"Piccini","sequence":"first","affiliation":[{"name":"Hematology Department, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-6501","authenticated-orcid":false,"given":"Francesco","family":"Mannelli","sequence":"additional","affiliation":[{"name":"Hematology Department, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy"},{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"CRIMM, Center for Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-5462","authenticated-orcid":false,"given":"Giacomo","family":"Coltro","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"CRIMM, Center for Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/ajh.25162","article-title":"Very poor long-term survival in past and more recent studies for relapsed AML patients: The ECOG-ACRIN experience","volume":"93","author":"Ganzel","year":"2018","journal-title":"Am. 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