{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Carter BZ"],"funding":["NCI NIH HHS"],"pagination":["1056-1070"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10656725"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["142(12)"],"pubmed_abstract":["TP 53-mutant acute myeloid leukemia (AML) remains the ultimate therapeutic challenge. Epichaperomes, formed in malignant cells, consist of heat shock protein 90 (HSP90) and associated proteins that support the maturation, activity, and stability of oncogenic kinases and transcription factors including mutant p53. High-throughput drug screening identified HSP90 inhibitors as top hits in isogenic TP53-wild-type (WT) and -mutant AML cells. We detected epichaperomes in AML cells and stem/progenitor cells with TP53 mutations but not in healthy bone marrow (BM) cells. Hence, we investigated the therapeutic potential of specifically targeting epichaperomes with PU-H71 in TP53-mutant AML based on its preferred binding to HSP90 within epichaperomes. PU-H71 effectively suppressed cell intrinsic stre"],"journal":["Blood"],"pubmed_title":["Epichaperome inhibition targets TP53-mutant AML and AML stem/progenitor cells."],"pmcid":["PMC10656725"],"funding_grant_id":["P30 CA016672"],"pubmed_authors":["Sobieski M","Bedoy AD","Basyal M","Muftuoglu M","Pei J","Ebert BL","Andreeff M","Powell RT","Shpall EJ","Isgandarova S","Carter BZ","Martinez-Moczygemba M","Stephan C","Boettcher S","Morgan RA","Karras GI","Nguyen N","Ostermann LB","Wallner B","Tao W","Pemmaraju N","Moll UM","Mak PY","Ke B","Nishida Y"],"additional_accession":[]},"is_claimable":false,"name":"Epichaperome inhibition targets TP53-mutant AML and AML stem/progenitor cells.","description":"TP 53-mutant acute myeloid leukemia (AML) remains the ultimate therapeutic challenge. Epichaperomes, formed in malignant cells, consist of heat shock protein 90 (HSP90) and associated proteins that support the maturation, activity, and stability of oncogenic kinases and transcription factors including mutant p53. High-throughput drug screening identified HSP90 inhibitors as top hits in isogenic TP53-wild-type (WT) and -mutant AML cells. We detected epichaperomes in AML cells and stem/progenitor cells with TP53 mutations but not in healthy bone marrow (BM) cells. Hence, we investigated the therapeutic potential of specifically targeting epichaperomes with PU-H71 in TP53-mutant AML based on its preferred binding to HSP90 within epichaperomes. PU-H71 effectively suppressed cell intrinsic stre","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Sep","modification":"2026-06-04T04:10:45.278Z","creation":"2025-04-04T11:34:24.809Z"},"accession":"S-EPMC10656725","cross_references":{"pubmed":["37339579"],"doi":["10.1182/blood.2022019047"]}}