{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:19:38Z","timestamp":1790741978115,"version":"4.1.0"},"reference-count":194,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009553","name":"Agentura Pro Zdravotnick\u00fd V\u00fdzkum \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["AZV NU21-03-00386"],"award-info":[{"award-number":["AZV NU21-03-00386"]}],"id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["GACR17-14007S and GACR19-08772S"],"award-info":[{"award-number":["GACR17-14007S and GACR19-08772S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["Center of Excellence UNCE\/MED\/016"],"award-info":[{"award-number":["Center of Excellence UNCE\/MED\/016"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","award":["PROGRES Q26\/LF1 and PROGRES Q28\/LF1"],"award-info":[{"award-number":["PROGRES Q26\/LF1 and PROGRES Q28\/LF1"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hematologic malignancies (HM) comprise diverse cancers of lymphoid and myeloid origin, including lymphomas (approx. 40%), chronic lymphocytic leukemia (CLL, approx. 15%), multiple myeloma (MM, approx. 15%), acute myeloid leukemia (AML, approx. 10%), and many other diseases. Despite considerable improvement in treatment options and survival parameters in the new millennium, many patients with HM still develop chemotherapy\u2011refractory diseases and require re-treatment. Because frontline therapies for the majority of HM (except for CLL) are still largely based on classical cytostatics, the relapses are often associated with defects in DNA damage response (DDR) pathways and anti-apoptotic blocks exemplified, respectively, by mutations or deletion of the TP53 tumor suppressor, and overexpression of anti-apoptotic proteins of the B-cell lymphoma 2 (BCL2) family. BCL2 homology 3 (BH3) mimetics represent a novel class of pro-apoptotic anti-cancer agents with a unique mode of action\u2014direct targeting of mitochondria independently of TP53 gene aberrations. Consequently, BH3 mimetics can effectively eliminate even non-dividing malignant cells with adverse molecular cytogenetic alterations. Venetoclax, the nanomolar inhibitor of BCL2 anti-apoptotic protein has been approved for the therapy of CLL and AML. Numerous venetoclax-based combinatorial treatment regimens, next-generation BCL2 inhibitors, and myeloid cell leukemia 1 (MCL1) protein inhibitors, which are another class of BH3 mimetics with promising preclinical results, are currently being tested in several clinical trials in patients with diverse HM. These pivotal trials will soon answer critical questions and concerns about these innovative agents regarding not only their anti-tumor efficacy but also potential side effects, recommended dosages, and the optimal length of therapy as well as identification of reliable biomarkers of sensitivity or resistance. Effective harnessing of the full therapeutic potential of BH3 mimetics is a critical mission as it may directly translate into better management of the aggressive forms of HM and could lead to significantly improved survival parameters and quality of life in patients with urgent medical needs.<\/jats:p>","DOI":"10.3390\/ijms221810157","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"10157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["BH3 Mimetics in Hematologic Malignancies"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7786-9378","authenticated-orcid":false,"given":"Pavel","family":"Klener","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine\u2011Hematology, General University Hospital in Prague, 121 08 Prague, Czech Republic"},{"name":"First Faculty of Medicine, Institute of Pathological Physiology, Charles University, 121 08 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8701-5912","authenticated-orcid":false,"given":"Dana","family":"Sovilj","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology CAS\/BIOCEV, 252 50 Vestec, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol","family":"Renesova","sequence":"additional","affiliation":[{"name":"First Faculty of Medicine, Institute of Pathological Physiology, Charles University, 121 08 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladislav","family":"Andera","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology CAS\/BIOCEV, 252 50 Vestec, Czech Republic"},{"name":"Institute of Molecular Genetics CAS, 142 20 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev-immunol-042617-053010","article-title":"Apoptosis and clearance of apoptotic cells","volume":"36","author":"Nagata","year":"2018","journal-title":"Annu. 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