2023
Computational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies
Li Q, Robinson M, Leveille E, Zhang C, Sun R, Cheng Z, Kume K, Cosgun K, Kothari S, Khanduja D, Nakada D, Müschen M. Computational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies. Blood 2023, 142: 418. DOI: 10.1182/blood-2023-190269.Peer-Reviewed Original ResearchSmall molecule inhibitorsDrug discovery toolNAMPT inhibitorsCompound screenCell type-specific targetsCell linesMolecule inhibitorsPurine/pyrimidine metabolismTumor cell linesEnergy metabolismSalvage biosynthesis pathwaySolid tumor cell linesB cell developmentCellular energy metabolismB cell signalingAmino acid metabolismCell cycle arrestDiscovery toolDepletion of metabolitesBiosynthesis pathwayCompetitive fitnessRate-limiting enzymeNAMPT deletionConditional mouse modelEnergy stress
2018
Divergent Evolutionary Trajectories of Erk- and Stat5-Activating Lesions in Acute Lymphoblastic Leukemia
Chan L, Shojaee S, Hurtz C, Auer F, Chen Z, Cosgun K, Geng H, Sadras T, White D, Muschen M. Divergent Evolutionary Trajectories of Erk- and Stat5-Activating Lesions in Acute Lymphoblastic Leukemia. Blood 2018, 132: 568. DOI: 10.1182/blood-2018-99-115536.Peer-Reviewed Original ResearchEvolutionary trajectoriesColony formation abilityCompetitive fitnessCommitment stepPre-B cell receptorDivergent evolutionary trajectoriesUpstream kinase MEKNormal B cell developmentOncogenic signal transductionInducible ablationActivation of STAT5B cell developmentEmpty vector controlActivation of ERKCentral oncogenic driverB-cell transformationImmature B cellsSignal transductionFormation abilityKinase MEKPhosphorylation of ERKGrowth factor receptorPatient-derived preAlternative pathwayERK activity