2021
PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis
Pan L, Hong C, Chan LN, Xiao G, Malvi P, Robinson ME, Geng H, Reddy ST, Lee J, Khairnar V, Cosgun KN, Xu L, Kume K, Sadras T, Wang S, Wajapeyee N, Müschen M. PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2016553118. PMID: 33531346, PMCID: PMC7896313, DOI: 10.1073/pnas.2016553118.Peer-Reviewed Original ResearchConceptsTransplant recipient miceDNA double-strand breaksNormal B cell developmentDouble-strand breaksB cell developmentGenetic deletionB cellsLymphoid transcription factorsGlucose transporter GLUT1Gatekeeper functionGlucose uptakeRecipient miceTranscription factorsSomatic recombinationSynthetic lethalityB-cell acute lymphoblastic leukemiaCell developmentMetabolic gatekeeperRefractory B-ALLDeficient murineCell acute lymphoblastic leukemiaPoor clinical outcomeCell typesAcute lymphoblastic leukemiaGlucose transport
2014
Gene Expression and Mutation Analysis (GEMA) –Guided Precision Medicine Targeting PARP1 to Induce Synthetic Lethality in DNA-PK –Deficient Quiescent and BRCA-Deficient Proliferating Leukemia Stem and Progenitor Cells
Nieborowska-Skorska M, Sullivan K, Podszywalow-Bartnicka P, Hoser G, Bolton-Gillespie E, Cramer-Morales K, Slupianek A, Zhou C, Cerny-Reiterer S, Stoklosa T, Sykes S, Valent P, Civin C, Muschen M, Minden M, Eppert K, Skorski T. Gene Expression and Mutation Analysis (GEMA) –Guided Precision Medicine Targeting PARP1 to Induce Synthetic Lethality in DNA-PK –Deficient Quiescent and BRCA-Deficient Proliferating Leukemia Stem and Progenitor Cells. Blood 2014, 124: 480. DOI: 10.1182/blood.v124.21.480.480.Peer-Reviewed Original ResearchQuiescent leukemia stem cellsLeukemia progenitor cellsLeukemia stem cellsIndividual patientsPARP1 inhibitorsBCR-ABL1MLL-AF9Progenitor cellsHomologous recombination repairSurvival of miceAML1-ETOAnti-tumor treatmentBone marrow cellsQuiescent cellsMutation analysisCML-CPDisease burdenImmunodeficient miceTumor initiatingLeukemia xenograftsReduced colony formationPatientsPharmacological inhibitionDNA double-strand breaksRepair mechanisms