{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Marshall A"],"funding":["Cancer Research UK","Children with Cancer UK","British Heart Foundation","Kay Kendall Leukaemia Fund","Medical Research Council","Crohn's & Colitis Foundation","Blood Cancer UK","Wellcome Trust","CHILDREN with CANCER UK","Japan Society for the Promotion of Science"],"pagination":["19390"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7656267"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(1)"],"pubmed_abstract":["AML is a genetically heterogeneous disease and understanding how different co-occurring mutations cooperate to drive leukemogenesis will be crucial for improving diagnostic and therapeutic options for patients. MIR142 mutations have been recurrently detected in IDH-mutated AML samples. Here, we have used a mouse model to investigate the interaction between these two mutations and demonstrate a striking synergy between Mir142 loss-of-function and IDH2<sup>R140Q</sup>, with only recipients of double mutant cells succumbing to leukemia. Transcriptomic analysis of the non-leukemic single and leukemic double mutant progenitors, isolated from these mice, suggested a novel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa cluster genes by IDH2<sup>R14"],"journal":["Scientific reports"],"pubmed_title":["Mir142 loss unlocks IDH2&lt;sup&gt;R140&lt;/sup&gt;-dependent leukemogenesis through antagonistic regulation of HOX genes."],"pmcid":["PMC7656267"],"funding_grant_id":["KKL889","16001","12796","PG/12/36/29444","639089","163011","JP16H06276","MR/N000838/1","C416/A20938","17-250","107387/Z/15/Z"],"pubmed_authors":["Deltcheva E","Nimmo R","Guo Y","James C","Kasturiarachchi J","May G","Khwaja A","Lord GM","Brooks S","Anandagoda N","Datta P","Ghazaly E","Marshall A","Brown J","Linch D","Araki M","Jackson I","Howard JK","Araki K","Enver T"],"additional_accession":[]},"is_claimable":false,"name":"Mir142 loss unlocks IDH2&lt;sup&gt;R140&lt;/sup&gt;-dependent leukemogenesis through antagonistic regulation of HOX genes.","description":"AML is a genetically heterogeneous disease and understanding how different co-occurring mutations cooperate to drive leukemogenesis will be crucial for improving diagnostic and therapeutic options for patients. MIR142 mutations have been recurrently detected in IDH-mutated AML samples. Here, we have used a mouse model to investigate the interaction between these two mutations and demonstrate a striking synergy between Mir142 loss-of-function and IDH2<sup>R140Q</sup>, with only recipients of double mutant cells succumbing to leukemia. Transcriptomic analysis of the non-leukemic single and leukemic double mutant progenitors, isolated from these mice, suggested a novel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa cluster genes by IDH2<sup>R14","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Nov","modification":"2026-05-07T16:25:34.034Z","creation":"2020-11-19T15:24:16Z"},"accession":"S-EPMC7656267","cross_references":{"pubmed":["33173219"],"doi":["10.1038/s41598-020-76218-8"]}}