{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ueda K"],"funding":["NHLBI NIH HHS","NCI NIH HHS","NIH","NIGMS NIH HHS"],"pagination":["529-547.e7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8575661"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["39(4)"],"pubmed_abstract":["MDMX is overexpressed in the vast majority of patients with acute myeloid leukemia (AML). We report that MDMX overexpression increases preleukemic stem cell (pre-LSC) number and competitive advantage. Utilizing five newly generated murine models, we found that MDMX overexpression triggers progression of multiple chronic/asymptomatic preleukemic conditions to overt AML. Transcriptomic and proteomic studies revealed that MDMX overexpression exerts this function, unexpectedly, through activation of Wnt/β-Catenin signaling in pre-LSCs. Mechanistically, MDMX binds CK1α and leads to accumulation of β-Catenin in a p53-independent manner. Wnt/β-Catenin inhibitors reverse MDMX-induced pre-LSC properties, and synergize with MDMX-p53 inhibitors. Wnt/β-Catenin signaling correlates with MDMX expression"],"journal":["Cancer cell"],"pubmed_title":["MDMX acts as a pervasive preleukemic-to-acute myeloid leukemia transition mechanism."],"pmcid":["PMC8575661"],"funding_grant_id":["R01 CA047296","P30 CA013330","F30 GM122308","R01 HL139487","T32 GM007288","R01 CA217092","R01 HL150832"],"pubmed_authors":["Narayanagari SR","Taylor SJ","Boultwood J","Wheat JC","Bartholdy B","Chen J","Shan J","Carvajal LA","Steidl U","Pradhan K","Xiong S","Pellagatti A","Goto H","Ueda K","Verma A","Lozano G","Sun D","Montagna C","Kumari R","Schwenger E","Todorova TI","Bohorquez O","Song Y"],"additional_accession":[]},"is_claimable":false,"name":"MDMX acts as a pervasive preleukemic-to-acute myeloid leukemia transition mechanism.","description":"MDMX is overexpressed in the vast majority of patients with acute myeloid leukemia (AML). We report that MDMX overexpression increases preleukemic stem cell (pre-LSC) number and competitive advantage. Utilizing five newly generated murine models, we found that MDMX overexpression triggers progression of multiple chronic/asymptomatic preleukemic conditions to overt AML. Transcriptomic and proteomic studies revealed that MDMX overexpression exerts this function, unexpectedly, through activation of Wnt/β-Catenin signaling in pre-LSCs. Mechanistically, MDMX binds CK1α and leads to accumulation of β-Catenin in a p53-independent manner. Wnt/β-Catenin inhibitors reverse MDMX-induced pre-LSC properties, and synergize with MDMX-p53 inhibitors. Wnt/β-Catenin signaling correlates with MDMX expression","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Apr","modification":"2026-05-09T03:09:39.912Z","creation":"2025-02-18T23:32:13.641Z"},"accession":"S-EPMC8575661","cross_references":{"pubmed":["33667384"],"doi":["10.1016/j.ccell.2021.02.006"]}}