biostudies-literatureUnknown17(2)Perzolli A<h4>Background</h4>Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that utilize the ubiquitin-proteasome system to selectively degrade target proteins. This innovative technology has shown remarkable efficacy and specificity in degrading oncogenic proteins and has progressed through various stages of preclinical and clinical development for hematologic malignancies, including adult acute myeloid leukemia (AML). However, the application of PROTACs in pediatric AML remains largely unexplored.<h4>Methods</h4>In this study, we show the potent effect of GSPT1 degradation against AML cells induced by either a GSPT1-selective cereblon modulator CC-90009 or by an off-target effect caused by a CDK6-PROTAC named GU3341.<h4>Results</h4>Both in vitro and ex vivo experimCancers211https://www.ebi.ac.uk/biostudies/studies/S-EPMC11763475biostudies-literaturePROTAC-Mediated GSPT1 Degradation Impairs the Expression of Fusion Genes in Acute Myeloid Leukemia.PMC11763475Gutschow MKronke JBarneh FPerzolli AZwaan CMSteinebach CHeidenreich OfalsePROTAC-Mediated GSPT1 Degradation Impairs the Expression of Fusion Genes in Acute Myeloid Leukemia.<h4>Background</h4>Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that utilize the ubiquitin-proteasome system to selectively degrade target proteins. This innovative technology has shown remarkable efficacy and specificity in degrading oncogenic proteins and has progressed through various stages of preclinical and clinical development for hematologic malignancies, including adult acute myeloid leukemia (AML). However, the application of PROTACs in pediatric AML remains largely unexplored.<h4>Methods</h4>In this study, we show the potent effect of GSPT1 degradation against AML cells induced by either a GSPT1-selective cereblon modulator CC-90009 or by an off-target effect caused by a CDK6-PROTAC named GU3341.<h4>Results</h4>Both in vitro and ex vivo experim2025-01-01T00:00:00Z2025 Jan2025-04-04T22:06:59.882Z2025-04-04T22:06:59.882ZS-EPMC117634753985799310.3390/cancers17020211