RNA Shielding of p65 Is Required to Potentiate Oncogenic Inflammation in TET2-Mutated Clonal Hematopoiesis

p65的RNA屏蔽对于增强TET2突变克隆性造血中的致癌炎症是必需的

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作者:Nana Adjoa Ben-Crentsil,Wazim Mohammed Ismail,Maria E Balasis,Hannah Newman,Ariel Quintana,Moritz Binder,Traci Kruer,Surendra Neupane,Meghan C Ferrall-Fairbanks,Jenna Fernandez,Terra L Lasho,Christy M Finke,Mohammed L Ibrahim,Kathy L McGraw,Michael Wysota,Amy L Aldrich,Christopher B Ryder,Christopher T Letson,Joshua Traina,Amy F McLemore,Nathalie Droin,Aditi Shastri,Seongseok Yun,Eric Solary,David A Sallman,Amer A Beg,Li Ma,Alexandre Gaspar-Maia,Mrinal M Patnaik,Eric Padron

Abstract

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.

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