{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:54:53Z","timestamp":1784735693219,"version":"3.55.0"},"reference-count":58,"publisher":"American Society of Hematology","issue":"12","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,9,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2013wild-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 stress responses and killed AML cells, primarily by inducing apoptosis; targeted TP53-mutant stem\/progenitor cells; and prolonged survival of TP53-mutant AML xenograft and patient-derived xenograft models, but it had minimal effects on healthy human BM CD34+ cells or on murine hematopoiesis. PU-H71 decreased MCL-1 and multiple signal proteins, increased proapoptotic Bcl-2-like protein 11 levels, and synergized with BCL-2 inhibitor venetoclax in TP53-mutant AML. Notably, PU-H71 effectively killed TP53-WT and -mutant cells in isogenic TP53-WT\/TP53-R248W Molm13 cell mixtures, whereas MDM2 or BCL-2 inhibition only reduced TP53-WT but favored the outgrowth of TP53-mutant cells. Venetoclax enhanced the killing of both TP53-WT and -mutant cells by PU-H71 in a xenograft model. Our data suggest that epichaperome function is essential for TP53-mutant AML growth and survival and that its inhibition targets mutant AML and stem\/progenitor cells, enhances venetoclax activity, and prevents the outgrowth of venetoclax-resistant TP53-mutant AML clones. These concepts warrant clinical evaluation.<\/jats:p>","DOI":"10.1182\/blood.2022019047","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T21:55:55Z","timestamp":1687298155000},"page":"1056-1070","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":28,"title":["Epichaperome inhibition targets <i>TP53-<\/i>mutant AML and AML stem\/progenitor cells"],"prefix":"10.1182","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-0889","authenticated-orcid":false,"given":"Bing Z.","family":"Carter","sequence":"first","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po Yee","family":"Mak","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muharrem","family":"Muftuoglu","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Tao","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baozhen","family":"Ke","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqi","family":"Pei","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4937-4527","authenticated-orcid":false,"given":"Andrea D.","family":"Bedoy","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3330-2174","authenticated-orcid":false,"given":"Lauren B.","family":"Ostermann","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Nishida","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevinj","family":"Isgandarova","sequence":"additional","affiliation":[{"name":"2Center for Infectious and Inflammatory Disease, Texas A&M University, Institute of Bioscience and Technology, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Sobieski","sequence":"additional","affiliation":[{"name":"3Center for Translational Cancer Research, Texas A&M University, Institute of Bioscience and Technology, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nghi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"3Center for Translational Cancer Research, Texas A&M University, Institute of Bioscience and Technology, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reid T.","family":"Powell","sequence":"additional","affiliation":[{"name":"3Center for Translational Cancer Research, Texas A&M University, Institute of Bioscience and Technology, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Martinez-Moczygemba","sequence":"additional","affiliation":[{"name":"2Center for Infectious and Inflammatory Disease, Texas A&M University, Institute of Bioscience and Technology, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0657-6484","authenticated-orcid":false,"given":"Clifford","family":"Stephan","sequence":"additional","affiliation":[{"name":"3Center for Translational Cancer Research, Texas A&M University, Institute of Bioscience and Technology, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Basyal","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1670-6513","authenticated-orcid":false,"given":"Naveen","family":"Pemmaraju","sequence":"additional","affiliation":[{"name":"4Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-0957","authenticated-orcid":false,"given":"Steffen","family":"Boettcher","sequence":"additional","affiliation":[{"name":"5Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-5451","authenticated-orcid":false,"given":"Benjamin L.","family":"Ebert","sequence":"additional","affiliation":[{"name":"6Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Shpall","sequence":"additional","affiliation":[{"name":"7Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Wallner","sequence":"additional","affiliation":[{"name":"8Samus Therapeutics Inc, Topsfield, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Morgan","sequence":"additional","affiliation":[{"name":"8Samus Therapeutics Inc, Topsfield, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2933-1535","authenticated-orcid":false,"given":"Georgios I.","family":"Karras","sequence":"additional","affiliation":[{"name":"9Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX"},{"name":"10Genetics and Epigenetics Graduate Program, The University of Texas MD Anderson Cancer Center, UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute M.","family":"Moll","sequence":"additional","affiliation":[{"name":"11Department of Pathology, Stony Brook University, Stony Brook, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-1958","authenticated-orcid":false,"given":"Michael","family":"Andreeff","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"7","key":"2023092719102425200_bib1","doi-asserted-by":"crossref","first-page":"e331","DOI":"10.1038\/bcj.2015.59","article-title":"TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution","volume":"5","author":"Hou","year":"2015","journal-title":"Blood Cancer J"},{"issue":"3","key":"2023092719102425200_bib2","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/leu.2016.263","article-title":"The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases","volume":"31","author":"Stengel","year":"2017","journal-title":"Leukemia"},{"issue":"22","key":"2023092719102425200_bib3","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1002\/cncr.30203","article-title":"TP53 mutations in newly diagnosed acute myeloid leukemia: clinicomolecular characteristics, response to therapy, and outcomes","volume":"122","author":"Kadia","year":"2016","journal-title":"Cancer"},{"issue":"22","key":"2023092719102425200_bib4","doi-asserted-by":"crossref","first-page":"5681","DOI":"10.1182\/bloodadvances.2020003120","article-title":"Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia","volume":"4","author":"Short","year":"2020","journal-title":"Blood Adv"},{"issue":"11","key":"2023092719102425200_bib5","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1182\/blood.2019003988","article-title":"Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML","volume":"135","author":"DiNardo","year":"2020","journal-title":"Blood"},{"issue":"20","key":"2023092719102425200_bib6","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1002\/cncr.33689","article-title":"Outcomes of TP53-mutant acute myeloid leukemia with decitabine and venetoclax","volume":"127","author":"Kim","year":"2021","journal-title":"Cancer"},{"issue":"7540","key":"2023092719102425200_bib7","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/nature13968","article-title":"Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia","volume":"518","author":"Wong","year":"2015","journal-title":"Nature"},{"issue":"4","key":"2023092719102425200_bib8","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/s41375-018-0279-6","article-title":"Histone deacetylase inhibitor targets CD123\/CD47-positive cells and reverse chemoresistance phenotype in acute myeloid leukemia","volume":"33","author":"Yan","year":"2019","journal-title":"Leukemia"},{"issue":"10","key":"2023092719102425200_bib9","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/nrc1716","article-title":"HSP90 and the chaperoning of cancer","volume":"5","author":"Whitesell","year":"2005","journal-title":"Nat Rev Cancer"},{"issue":"7","key":"2023092719102425200_bib10","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/nrm2918","article-title":"HSP90 at the hub of protein homeostasis: emerging mechanistic insights","volume":"11","author":"Taipale","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"7625","key":"2023092719102425200_bib11","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nature19807","article-title":"The epichaperome is an integrated chaperome network that facilitates tumour survival","volume":"538","author":"Rodina","year":"2016","journal-title":"Nature"},{"issue":"5","key":"2023092719102425200_bib12","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ccell.2019.09.007","article-title":"Paradigms for precision medicine in epichaperome cancer therapy","volume":"36","author":"Pillarsetty","year":"2019","journal-title":"Cancer Cell"},{"issue":"11","key":"2023092719102425200_bib13","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/nchembio.670","article-title":"Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90","volume":"7","author":"Moulick","year":"2011","journal-title":"Nat Chem Biol"},{"issue":"12","key":"2023092719102425200_bib14","first-page":"4483","article-title":"FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinases","volume":"9","author":"Yao","year":"2003","journal-title":"Clin Cancer Res"},{"issue":"2","key":"2023092719102425200_bib15","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1182\/blood-2006-04-019141","article-title":"SHP-2 phosphatase is required for hematopoietic cell transformation by Bcr-Abl","volume":"109","author":"Chen","year":"2007","journal-title":"Blood"},{"issue":"7","key":"2023092719102425200_bib16","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/j.1745-7270.2005.00069.x","article-title":"Heat shock protein 90 indirectly regulates ERK activity by affecting Raf protein metabolism","volume":"37","author":"Dou","year":"2005","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"issue":"3","key":"2023092719102425200_bib17","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2174\/138161213804143725","article-title":"The therapeutic target Hsp90 and cancer hallmarks","volume":"19","author":"Miyata","year":"2013","journal-title":"Curr Pharm Des"},{"issue":"7560","key":"2023092719102425200_bib18","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nature14430","article-title":"Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment","volume":"523","author":"Alexandrova","year":"2015","journal-title":"Nature"},{"issue":"10","key":"2023092719102425200_bib19","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/nsmb.2114","article-title":"Structural analysis of the interaction between Hsp90 and the tumor suppressor protein p53","volume":"18","author":"Hagn","year":"2011","journal-title":"Nat Struct Mol Biol"},{"issue":"4","key":"2023092719102425200_bib20","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/j.1600-0609.2012.01825.x","article-title":"Expression of phosphorylated signal transducer and activator of transcription 5 is associated with an increased risk of death in acute myeloid leukemia","volume":"89","author":"Brady","year":"2012","journal-title":"Eur J Haematol"},{"issue":"4","key":"2023092719102425200_bib21","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/00062752-200207000-00003","article-title":"Role of FLT3 in leukemia","volume":"9","author":"Gilliland","year":"2002","journal-title":"Curr Opin Hematol"},{"issue":"7","key":"2023092719102425200_bib22","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1182\/blood-2006-02-003475","article-title":"Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia","volume":"108","author":"Kornblau","year":"2006","journal-title":"Blood"},{"issue":"2","key":"2023092719102425200_bib23","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1158\/0008-5472.CAN-06-3166","article-title":"Activation of integrin-linked kinase is a critical prosurvival pathway induced in leukemic cells by bone marrow-derived stromal cells","volume":"67","author":"Tabe","year":"2007","journal-title":"Cancer Res"},{"issue":"suppl 1","key":"2023092719102425200_bib24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1182\/blood-2020-142993","article-title":"JAK\/STAT inhibition targets TP53 altered primary human acute myeloid leukemia stem cells [abstract]","volume":"136","author":"Antony","year":"2020","journal-title":"Blood"},{"issue":"2","key":"2023092719102425200_bib25","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.ccell.2018.07.004","article-title":"Therapeutic ablation of gain-of-function mutant p53 in colorectal cancer inhibits stat3-mediated tumor growth and invasion","volume":"34","author":"Schulz-Heddergott","year":"2018","journal-title":"Cancer Cell"},{"issue":"22","key":"2023092719102425200_bib26","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1182\/bloodadvances.2019001068","article-title":"LAM-003, a new drug for treatment of tyrosine kinase inhibitor-resistant FLT3-ITD-positive AML","volume":"3","author":"Beeharry","year":"2019","journal-title":"Blood Adv"},{"issue":"9","key":"2023092719102425200_bib27","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1038\/s41375-021-01308-z","article-title":"Inhibition of translation initiation factor eIF4a inactivates heat shock factor 1 (HSF1) and exerts anti-leukemia activity in AML","volume":"35","author":"Nishida","year":"2021","journal-title":"Leukemia"},{"issue":"4","key":"2023092719102425200_bib28","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s12192-018-0877-2","article-title":"Methods to validate Hsp90 inhibitor specificity, to identify off-target effects, and to rethink approaches for further clinical development","volume":"23","author":"Neckers","year":"2018","journal-title":"Cell Stress Chaperones"},{"issue":"7","key":"2023092719102425200_bib29","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1182\/blood-2015-05-645069","article-title":"Combinatorial targeting of nuclear export and translation of RNA inhibits aggressive B-cell lymphomas","volume":"127","author":"Culjkovic-Kraljacic","year":"2016","journal-title":"Blood"},{"issue":"7369","key":"2023092719102425200_bib30","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/478334b","article-title":"Chemical biology: many faces of a cancer-supporting protein","volume":"478","author":"Darby","year":"2011  19","journal-title":"Nature"},{"issue":"12","key":"2023092719102425200_bib31","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1172\/JCI80714","article-title":"Pharmacoproteomics identifies combinatorial therapy targets for diffuse large B cell lymphoma","volume":"125","author":"Goldstein","year":"2015","journal-title":"J\u00a0Clin Invest"},{"issue":"22","key":"2023092719102425200_bib32","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1182\/blood-2015-03-635821","article-title":"Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias","volume":"126","author":"Kucine","year":"2015","journal-title":"Blood"},{"issue":"16","key":"2023092719102425200_bib33","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1182\/blood-2013-01-479972","article-title":"Targeting the Hsp90-associated viral oncoproteome in gammaherpesvirus-associated malignancies","volume":"122","author":"Nayar","year":"2013","journal-title":"Blood"},{"issue":"11","key":"2023092719102425200_bib34","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.tips.2014.09.001","article-title":"Selective targeting of the stress chaperome as a therapeutic strategy","volume":"35","author":"Taldone","year":"2014","journal-title":"Trends Pharmacol Sci"},{"issue":"10","key":"2023092719102425200_bib35","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1016\/j.celrep.2015.10.073","article-title":"A\u00a0hyperactive signalosome in acute myeloid leukemia drives addiction to a tumor-specific Hsp90 species","volume":"13","author":"Zong","year":"2015","journal-title":"Cell Rep"},{"issue":"19","key":"2023092719102425200_bib36","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1158\/1078-0432.CCR-19-3704","article-title":"First-in-human trial of epichaperome-targeted PET in patients with cancer","volume":"26","author":"Dunphy","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"2","key":"2023092719102425200_bib37","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s10637-017-0495-3","article-title":"First-in-human study of the epichaperome inhibitor PU-H71: clinical results and metabolic profile","volume":"36","author":"Speranza","year":"2018","journal-title":"Invest New Drugs"},{"issue":"suppl 1","key":"2023092719102425200_bib38","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.1182\/blood-2019-130310","article-title":"Phase 1b study of the epichaperome inhibitor PU-H71 administered orally with ruxolitinib continuation for the treatment of patients with myelofibrosis [abstract]","volume":"134","author":"Pemmaraju","year":"2019","journal-title":"Blood"},{"issue":"1","key":"2023092719102425200_bib39","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41698-021-00183-2","article-title":"Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia","volume":"5","author":"Sugita","year":"2021","journal-title":"NPJ Precis Oncol"},{"issue":"suppl 1","key":"2023092719102425200_bib40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1182\/blood-2020-142794","article-title":"Clonal expansion of mutant p53 clones by MDM2 inhibition in acute myeloid leukemias [abstract]","volume":"136","author":"Nishida","year":"2020","journal-title":"Blood"},{"issue":"6","key":"2023092719102425200_bib41","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.ccell.2017.11.003","article-title":"Synthetic lethality of combined Bcl-2 inhibition and p53 activation in AML: mechanisms and superior antileukemic efficacy","volume":"32","author":"Pan","year":"2017","journal-title":"Cancer Cell"},{"issue":"6453","key":"2023092719102425200_bib42","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1126\/science.aax3649","article-title":"A\u00a0dominant-negative effect drives selection of TP53 missense mutations in myeloid malignancies","volume":"365","author":"Boettcher","year":"2019","journal-title":"Science"},{"issue":"13","key":"2023092719102425200_bib43","first-page":"3603","article-title":"Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors","volume":"62","author":"Studeny","year":"2002","journal-title":"Cancer Res"},{"issue":"1","key":"2023092719102425200_bib44","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3324\/haematol.2020.260331","article-title":"Targeting MCL-1 dysregulates cell metabolism and\u00a0leukemia-stroma interactions and resensitizes acute myeloid leukemia to BCL-2 inhibition","volume":"107","author":"Carter","year":"2020","journal-title":"Haematologica"},{"issue":"7","key":"2023092719102425200_bib62","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1158\/0008-5472.CAN-05-1278","article-title":"Simultaneous Inhibition of PDK1\/AKT and Fms-Like Tyrosine Kinase 3 Signaling by a Small-Molecule KP372-1 Induces Mitochondrial Dysfunction and Apoptosis in Acute Myelogenous Leukemia","volume":"66","author":"Zeng","year":"2006","journal-title":"Cancer Res"},{"key":"2023092719102425200_bib47","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/bs.mie.2020.04.057","article-title":"Chemical probes and methods for single-cell detection and quantification of epichaperomes in hematologic malignancies","volume":"639","author":"Merugu","year":"2020","journal-title":"Methods Enzymol"},{"issue":"6","key":"2023092719102425200_bib48","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1158\/1535-7163.MCT-21-0690","article-title":"Maximal activation of apoptosis signaling by cotargeting antiapoptotic proteins in BH3 mimetic-resistant AML and AML stem cells","volume":"21","author":"Carter","year":"2022","journal-title":"Mol Cancer Ther"},{"issue":"8","key":"2023092719102425200_bib49","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1158\/1535-7163.MCT-19-0841","article-title":"Combinatorial inhibition of focal adhesion kinase and BCL-2 enhances antileukemia activity of venetoclax in acute myeloid leukemia","volume":"19","author":"Wang","year":"2020","journal-title":"Mol Cancer Ther"},{"issue":"suppl 1","key":"2023092719102425200_bib50","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1182\/blood-2020-143371","article-title":"High dimensional interrogation of stress response patterns and cell death modes in AML [abstract]","volume":"136","author":"Muftuoglu","year":"2020","journal-title":"Blood"},{"issue":"5-6","key":"2023092719102425200_bib52","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10495-019-01528-w","article-title":"Simultaneous polychromatic flow cytometric detection of multiple forms of regulated cell death","volume":"24","author":"Bergamaschi","year":"2019","journal-title":"Apoptosis"},{"key":"2023092719102425200_bib53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv Enzyme Regul"},{"issue":"suppl 1","key":"2023092719102425200_bib54","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1182\/blood-2019-131784","article-title":"Single-cell mapping of stress response and cell death pathways in acute myeloid leukemia reveals stressor-specific alterations and distinct response patterns [abstract]","volume":"134","author":"Muftuoglu","year":"2019","journal-title":"Blood"},{"key":"2023092719102425200_bib55","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fendo.2015.00053","article-title":"Mutant p53 - heat shock response oncogenic cooperation: a new mechanism of cancer cell survival","volume":"6","author":"Alexandrova","year":"2015","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2023092719102425200_bib56","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.3389\/fonc.2020.01102","article-title":"STAT3 and mutp53 engage a positive feedback loop involving HSP90 and the mevalonate pathway","volume":"10","author":"Romeo","year":"2020","journal-title":"Front Oncol"},{"issue":"6","key":"2023092719102425200_bib57","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.bbamcr.2013.02.014","article-title":"Hsp90 inhibition by PU-H71 induces apoptosis through endoplasmic reticulum stress and mitochondrial pathway in cancer cells and overcomes the resistance conferred by Bcl-2","volume":"1833","author":"Gallerne","year":"2013","journal-title":"Biochim Biophys Acta"},{"issue":"11","key":"2023092719102425200_bib58","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.21873\/anticanres.14634","article-title":"Heat shock protein 90 inhibitors AUY922, BIIB021 and SNX5422 induce bim-mediated death of thyroid carcinoma cells","volume":"40","author":"Kim","year":"2020","journal-title":"Anticancer Res"},{"issue":"2","key":"2023092719102425200_bib59","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0014-5793(99)01359-9","article-title":"Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction","volume":"460","author":"Minet","year":"1999","journal-title":"FEBS Lett"},{"issue":"10","key":"2023092719102425200_bib60","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1038\/s41388-020-1201-z","article-title":"Therapeutic targeting of TP53-mutated acute myeloid leukemia by inhibiting HIF-1\u03b1 with echinomycin","volume":"11","author":"Wang","year":"2020","journal-title":"Oncogene"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/142\/12\/1056\/2081341\/blood_bld-2022-019047-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/142\/12\/1056\/2081341\/blood_bld-2022-019047-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T19:10:51Z","timestamp":1695841851000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/142\/12\/1056\/496472\/Epichaperome-inhibition-targets-TP53-mutant-AML"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,21]]},"references-count":58,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,9,21]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2022019047","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,21]]}}}