Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia Journal Article

  

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Authors:	Glaviano, A.; Weisberg, E.; Lam, H. Y.; Tan, D. J. J.; Innes, A. J.; Ge, Y. B.; Lai, C. E.; Stock, W.; Glytsou, C.; Smit, L.; Yoshida, T.; Zhang, T. Y.; Kennedy, V. E.; Smith, B. D.; Mercher, T.; de Botton, S.; Diana, P.; Konopleva, M.; Mauro, M. J.; Griffin, J. D.; Dinardo, C. D.; Kumar, A. P.
Article Title:	Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia
Abstract:	<p>Acute myeloid leukaemia (AML) remains a challenging haematological malignancy, with most patients developing resistance to standard-of-care (SOC) treatments. This resistance is often attributed to the overexpression of anti-apoptotic BCL-2 family proteins, which regulate the intrinsic apoptotic pathway by inhibiting pro-apoptotic effector proteins such as BAX and BAK. AML cells exploit this imbalance to evade apoptosis and sustain survival, necessitating the development of novel therapeutic strategies. BH3 mimetics are small-molecule inhibitors targeting the pro-survival BCL-2 family proteins and have emerged as promising agents in patients with AML who are unable to receive high-intensity induction chemotherapy. Co-treatment with the BCL-2-specific inhibitor venetoclax and various SOC therapies has been proven effective, with several combinations now approved by the US Food and Drug Administration for adults with AML who are >= 75 years of age and/or are ineligible for intensive induction chemotherapy, on the basis of improved response rates and survival outcomes compared with the previous SOC. In this Review, we highlight the transformative potential of BH3 mimetics in AML therapy, including ongoing studies investigating novel combination regimens and efforts to further refine treatment strategies, with the ultimate goal of improving outcomes for patients with AML.</p>
Keywords:	resistance; cell-death; inhibition; mcl-1; high expression; daunorubicin-induced apoptosis; bcl-2 family proteins; abt-199; venetoclax-based therapy; aml cells
Journal Title:	Nature Reviews Clinical Oncology
ISSN:	1759-4774
Publisher:	Nature Publishing Group
Publication status:	Online ahead of print
Date Published:	2025-01-01
Online Publication Date:	2025-01-01
Language:	English
ACCESSION:	WOS:001564956300001
DOI:	10.1038/s41571-025-01068-0
PROVIDER:	wos
Notes:	Review; Early Access -- Source: Wos

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