biostudies-literatureBen-Crentsil NANational Cancer Institute (NCI)Moffitt Cancer Center (MCC)Moffitt Cancer CenterNational Cancer InstituteNCI NIH HHS2509-2531https://www.ebi.ac.uk/biostudies/studies/S-EPMC11611684biostudies-literatureUnknown14(12)<h4>Significance</h4>This work identifies MALAT1 as a requisite downstream effector of oncogenic feedforward inflammatory circuits necessary for the development of TET2-mutated CH and fulminant myeloid malignancy. We elucidate a novel mechanism by which MALAT1 "shields" p65 from dephosphorylation to potentiate this circuit and nominate MALAT1 inhibition as a future therapeutic strategy.Cancer discoveryRNA Shielding of p65 Is Required to Potentiate Oncogenic Inflammation in TET2-Mutated Clonal Hematopoiesis.PMC116116841R21CA216757-01A1P30-CA076292P30 CA076292R21 CA216757Beg AAMa LAldrich ALTraina JMohammed Ismail WNeupane SLasho TLIbrahim MLGaspar-Maia ABinder MSallman DAPadron EBalasis MEWysota MMcLemore AFQuintana AFinke CMFernandez JBen-Crentsil NADroin NNewman HRyder CBMcGraw KLSolary EKruer TShastri AYun SFerrall-Fairbanks MCLetson CTPatnaik MMfalseRNA Shielding of p65 Is Required to Potentiate Oncogenic Inflammation in TET2-Mutated Clonal Hematopoiesis.<h4>Significance</h4>This work identifies MALAT1 as a requisite downstream effector of oncogenic feedforward inflammatory circuits necessary for the development of TET2-mutated CH and fulminant myeloid malignancy. We elucidate a novel mechanism by which MALAT1 "shields" p65 from dephosphorylation to potentiate this circuit and nominate MALAT1 inhibition as a future therapeutic strategy.2024-01-01T00:00:00Z2024 Dec2026-06-02T08:54:10.475Z2026-04-16T03:12:46.036ZS-EPMC116116843918961410.1158/2159-8290.cd-24-009310.1158/2159-8290.CD-24-0093