2019
Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial
Brunner A, Blonquist T, DeAngelo D, McMasters M, Fell G, Hermance N, Winer E, Lindsley R, Hobbs G, Amrein P, Hock H, Steensma D, Garcia J, Luskin M, Stone R, Ballen K, Rosenblatt J, Avigan D, Nahas M, Mendez L, McAfee S, Moran J, Bergeron M, Foster J, Bertoli C, Manning A, McGregor K, Fishman K, Kuo F, Baltay M, Macrae M, Burke M, Behnan T, Wey M, Som T, Ramos A, Rae J, Lombardi Story J, Nelson N, Logan E, Connolly C, Neuberg D, Chen Y, Graubert T, Fathi A. Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial. The Lancet Haematology 2019, 7: e122-e133. PMID: 31837959, DOI: 10.1016/s2352-3026(19)30203-0.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaHigh-risk acute myeloid leukemiaTherapy-related acute myeloid leukemiaSecondary acute myeloid leukemiaPhase 2 trialPlatelet count recoveryInduction chemotherapyComplete remissionMyeloid leukemiaUntreated patientsEligible patientsCount recoveryDana-Farber/Harvard Cancer CenterEastern Cooperative Oncology Group performance statusUntreated acute myeloid leukemiaActivity of alisertibAdverse-risk karyotypeCommon grade 3Previous myelodysplastic syndromeTreatment-related deathsProportion of patientsPromising therapeutic targetComposite remissionFebrile neutropeniaOral alisertib
2017
MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs
Pyzer AR, Stroopinsky D, Rosenblatt J, Anastasiadou E, Rajabi H, Washington A, Tagde A, Chu JH, Coll M, Jiao AL, Tsai LT, Tenen DE, Cole L, Palmer K, Ephraim A, Leaf RK, Nahas M, Apel A, Bar-Natan M, Jain S, McMasters M, Mendez L, Arnason J, Raby BA, Slack F, Kufe D, Avigan D. MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs. Leukemia 2017, 31: 2780-2790. PMID: 28555079, PMCID: PMC5791150, DOI: 10.1038/leu.2017.163.Peer-Reviewed Original ResearchConceptsPD-L1 expressionAcute myeloid leukemiaAML cellsMiR-200cPD-L1/PDT cell-mediated lysisPD-L1 mRNA levelsLeukemia-specific T cellsPD-L1 levelsAnti-tumor immunityImmunosuppressive tumor microenvironmentMurine AML modelHuman AML cellsAML cell linesPotential therapeutic targetMicroRNA miR-200cMiR-34a levelsNanostring arraysMyeloid leukemiaT cellsTherapeutic targetMUC1 inhibitionTumor microenvironmentAML modelUpregulation of miRNAsMUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia.
Pyzer A, Stroopinsky D, Rajabi H, Washington A, Tagde A, Coll M, Fung J, Bryant M, Cole L, Palmer K, Somaiya P, Karp Leaf R, Nahas M, Apel A, Jain S, McMasters M, Mendez L, Levine J, Joyce R, Arnason J, Pandolfi P, Kufe D, Rosenblatt J, Avigan D. MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia. Blood 2017, 129: 1791-1801. PMID: 28126925, PMCID: PMC5813734, DOI: 10.1182/blood-2016-07-730614.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaSuppressor cellsAML cellsMyeloid leukemiaExtracellular vesiclesDonor peripheral blood mononuclear cellsAutologous T cell responsesCompetent antigen-presenting cellsMyeloid-derived suppressor cellsPeripheral blood mononuclear cellsReduced T-cell proliferationPresence of MDSCsExpansion of MDSCsT cell responsesBlood mononuclear cellsAntigen-presenting cellsPrimary AML cellsT cell proliferationExpansion of CD11bTumor-derived extracellular vesiclesMyeloid progenitor cellsMDSC populationsMDSC expansionImmune toleranceC57BL/6 mice