{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Thijssen R"],"funding":["Swiss National Science Foundation"],"pagination":["2721-2735"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8138548"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["137(20)"],"pubmed_abstract":["Selective targeting of BCL-2 with the BH3-mimetic venetoclax has been a transformative treatment for patients with various leukemias. TP-53 controls apoptosis upstream of where BCL-2 and its prosurvival relatives, such as MCL-1, act. Therefore, targeting these prosurvival proteins could trigger apoptosis across diverse blood cancers, irrespective of TP53 mutation status. Indeed, targeting BCL-2 has produced clinically relevant responses in blood cancers with aberrant TP-53. However, in our study, TP53-mutated or -deficient myeloid and lymphoid leukemias outcompeted isogenic controls with intact TP-53, unless sufficient concentrations of BH3-mimetics targeting BCL-2 or MCL-1 were applied. Strikingly, tumor cells with TP-53 dysfunction escaped and thrived over time if inhibition of BCL-2 or "],"journal":["Blood"],"pubmed_title":["Intact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias."],"pmcid":["PMC8138548"],"funding_grant_id":["180807"],"pubmed_authors":["Litalien V","Kallies A","Pomilio G","Reljic B","Gabriel SS","Strasser A","MacRaild S","Riffkin CD","Djajawi TM","Bajel A","Majewski IJ","Wei AH","Chang C","Schoumacher M","Morley T","Chew E","Moujalled D","Lane SW","Kelly GL","Tai L","Diepstraten ST","Dengler MA","Chen M","Thijssen R","Anstee NS","Aubrey BJ","Bruedigam C","Banquet S","Huang DCS","Stroud DA","Brown FC","Shi MX","Kluck RM","Flensburg C","Xu Z","Roberts AW"],"additional_accession":[]},"is_claimable":false,"name":"Intact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias.","description":"Selective targeting of BCL-2 with the BH3-mimetic venetoclax has been a transformative treatment for patients with various leukemias. TP-53 controls apoptosis upstream of where BCL-2 and its prosurvival relatives, such as MCL-1, act. Therefore, targeting these prosurvival proteins could trigger apoptosis across diverse blood cancers, irrespective of TP53 mutation status. Indeed, targeting BCL-2 has produced clinically relevant responses in blood cancers with aberrant TP-53. However, in our study, TP53-mutated or -deficient myeloid and lymphoid leukemias outcompeted isogenic controls with intact TP-53, unless sufficient concentrations of BH3-mimetics targeting BCL-2 or MCL-1 were applied. Strikingly, tumor cells with TP-53 dysfunction escaped and thrived over time if inhibition of BCL-2 or ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 May","modification":"2026-06-11T04:03:45.863Z","creation":"2022-02-11T14:14:48.64Z"},"accession":"S-EPMC8138548","cross_references":{"pubmed":["33824975"],"doi":["10.1182/blood.2020010167"]}}