2022
Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations
Choudhary GS, Pellagatti A, Agianian B, Smith MA, Bhagat TD, Gordon-Mitchell S, Sahu S, Pandey S, Shah N, Aluri S, Aggarwal R, Aminov S, Schwartz L, Steeples V, Booher RN, Ramachandra M, Samson M, Carbajal M, Pradhan K, Bowman TV, Pillai MM, Will B, Wickrema A, Shastri A, Bradley RK, Martell RE, Steidl UG, Gavathiotis E, Boultwood J, Starczynowski DT, Verma A. Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations. ELife 2022, 11: e78136. PMID: 36040792, PMCID: PMC9427103, DOI: 10.7554/elife.78136.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeNF-kB activationLymphoma SocietyMDS/acute myeloid leukemiaNational InstitutePathogenesis of MDSInterleukin-1 receptor-associated kinase 4Expression of IRAK4Inflammatory-immune pathwaysInflammatory cytokine productionSpecific oncogenic pathwaysCareer development grantsHealth research trainingCritical downstream mediatorCytokine productionMyeloid leukemiaPreclinical modelsNew York State DepartmentXenograft modelImmune pathwaysNF-kB.MDS samplesTRAF6 activationLeukemic growth
2019
SF3B1 Mutations Induce Oncogenic IRAK4 Isoforms and Activate Targetable Innate Immune Pathways in MDS and AML
Choudhary G, Smith M, Pellagatti A, Bhagat T, Gordon S, Pandey S, Shah N, Aluri S, Booher R, Ramachandra M, Samson M, Pradhan K, Bowman T, Pillai M, Guha C, Wickrema A, Will B, Shastri A, Steidl U, Boultwood J, Starczynowski D, Verma A. SF3B1 Mutations Induce Oncogenic IRAK4 Isoforms and Activate Targetable Innate Immune Pathways in MDS and AML. Blood 2019, 134: 4224. DOI: 10.1182/blood-2019-124458.Peer-Reviewed Original ResearchToll-like receptorsAML cellsSF3B1 mutationsMDS/AML cellsInterleukin-1 Receptor-Associated KinaseMDS/AMLNF-kB activityInnate immune pathwaysInnate immune signalingNormal cellsDownstream oncogenic pathwaysLeukemic burdenCytokine releaseIRAK4 expressionNF-kBAML samplesImmune pathwaysSmall molecule inhibitorsNovartis PharmaceuticalsLeukemic cellsExon 6Mutation showTRAF6 activationAMLPharmacologic inhibition