2016
Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin
Elf S, Lin R, Xia S, Pan Y, Shan C, Wu S, Lonial S, Gaddh M, Arellano M, Khoury H, Khuri F, Lee B, Boggon T, Fan J, Chen J. Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin. Oncogene 2016, 36: 254-262. PMID: 27270429, PMCID: PMC5464402, DOI: 10.1038/onc.2016.196.Peer-Reviewed Original ResearchConceptsLeukemia cellsTumor growthAntimalarial drugsNon-immune hemolytic anemiaCombined treatmentHealthy human donorsLeukemia cell viabilityXenograft nude micePrimary leukemia cellsNormal hematopoietic cellsCell viabilityHuman K562 leukemia cellsCancer cell metabolismRed blood cellsCombined therapyHemolytic anemiaAntileukemia treatmentClinical observationsNude miceHuman patientsHuman donorsAnticancer effectsK562 leukemia cellsMinimal toxicityDihydroartemisinin
2012
Phosphoglycerate Mutase 1 Promotes Leukemia Metabolism by Coordinating Glycolysis and Biosynthesis, and Represnts a Therapuetic Target in Leukemia Treatment
Hitosugi T, Zhou L, Fan J, Arellano M, Khoury H, Lee B, Boggon T, Kang S, He C, Chen J. Phosphoglycerate Mutase 1 Promotes Leukemia Metabolism by Coordinating Glycolysis and Biosynthesis, and Represnts a Therapuetic Target in Leukemia Treatment. Blood 2012, 120: 860. DOI: 10.1182/blood.v120.21.860.860.Peer-Reviewed Original ResearchPhosphoglycerate mutase 1Pentose phosphate pathwayHuman leukemia cell linesCell proliferationAnabolic biosynthesisCell metabolismLeukemia cell linesOxidative pentose phosphate pathwayPrimary leukemia cellsLeukemia cellsCancer cellsCell linesGlycolytic enzyme phosphoglycerate mutase 1PGAM1 inhibitorsSmall molecule inhibitorsCo-crystal structureXenograft nude miceInhibits cell proliferationLeukemia cell metabolismBiosynthesis pathwayEnzyme activity levelsHuman leukemia cellsShRNA resultsLoss of TP53Phosphate pathway
2010
Leukemogenic Tyrosine Kinases Inhibit PKM2 to Promote the Warburg Effect and Tumor Growth
Hitosugi T, Kang S, Vander Heiden M, Chung T, Elf S, Lythgoe K, Dong S, Lonial S, Wang X, Chen G, Xie J, Gu T, Polakiewicz R, Roesel J, Boggon T, Khuri F, Gilliland D, Cantley L, Kaufman J, Chen J. Leukemogenic Tyrosine Kinases Inhibit PKM2 to Promote the Warburg Effect and Tumor Growth. Blood 2010, 116: 3142. DOI: 10.1182/blood.v116.21.3142.3142.Peer-Reviewed Original ResearchCancer cell metabolismTumor growthTyrosine kinaseWarburg effectCancer cellsMolecular mechanismsOxidative phosphorylationReduced lactate productionCell metabolismLeukemia cellsPyruvate kinase M2 isoformLeukemogenic tyrosine kinasesPhosphorylation of PKM2RNAi-mediated knockdownXenograft nude micePhospho-proteomics studiesInhibition of PKM2Leukemia/lymphoma syndromeHypoxia-inducible factor-1Oncogenic tyrosine kinasesTyrosine kinase pathwayGrowth factor receptorInducible factor-1Phosphotyrosine bindingDisease progression