2023
CXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis
Dunbar A, Kim D, Lu M, Farina M, Bowman R, Yang J, Park Y, Karzai A, Xiao W, Zaroogian Z, O’Connor K, Mowla S, Gobbo F, Verachi P, Martelli F, Sarli G, Xia L, Elmansy N, Kleppe M, Chen Z, Xiao Y, McGovern E, Snyder J, Krishnan A, Hill C, Cordner K, Zouak A, Salama M, Yohai J, Tucker E, Chen J, Zhou J, McConnell T, Migliaccio A, Koche R, Rampal R, Fan R, Levine R, Hoffman R. CXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis. Blood 2023, 141: 2508-2519. PMID: 36800567, PMCID: PMC10273167, DOI: 10.1182/blood.2022015418.Peer-Reviewed Original ResearchConceptsConstitutive JAK/STATHematopoietic stem/progenitor cellsJAK/STATBone marrow fibrosisStem/progenitor cellsMPN cellsMarrow fibrosisHuman cancersMyeloproliferative neoplasmsPrimary cellsProgenitor cellsMechanistic insightsPharmacologic inhibitionGenetic deletionSignaling contributesGene signatureJAK inhibitor therapyTherapeutic targetingEnhanced proliferationCritical roleTherapeutic targetCXCL8/MF developmentMF pathogenesisInhibitor therapy
2021
3018 – SECRETORY MPP3 ENFORCE MYELOID DIFFERENTIATION TRAJECTORY AND AMPLIFY MYELOID CELL PRODUCTION
Kang Y, Paik H, Zhang S, Chen J, Warr M, Fan R, Passegué E. 3018 – SECRETORY MPP3 ENFORCE MYELOID DIFFERENTIATION TRAJECTORY AND AMPLIFY MYELOID CELL PRODUCTION. Experimental Hematology 2021, 100: s52. DOI: 10.1016/j.exphem.2021.12.240.Peer-Reviewed Original ResearchMyeloid cell productionBA miceMyeloid differentiationCell productionDonor chimerismSurvival benefitCytokine productionMolecular subsetsInflammatory stimuliMouse modelSpecific cytokinesMyeloid malignanciesMyeloproliferative neoplasmsDifferentiation cytokinesImmature cellsGalectin-3Disease conditionsMetabolic activationColony formationAberrant functionCytokinesConstitutive secretionMiceER volumeBlood production
2020
Increased Interleukin-8 (IL8)-CXCR2 Signaling Promotes Progression of Bone Marrow Fibrosis in Myeloproliferative Neoplasms
Dunbar A, Lu M, Farina M, Park Y, Yang J, Kim D, Karzai A, Salama M, Snyder J, Krishnan A, Koche R, Fan R, Levine R, Hoffman R. Increased Interleukin-8 (IL8)-CXCR2 Signaling Promotes Progression of Bone Marrow Fibrosis in Myeloproliferative Neoplasms. Blood 2020, 136: 6-7. DOI: 10.1182/blood-2020-138843.Peer-Reviewed Original ResearchCurrent equity holderMF patientsInterleukin-8Overall survivalReticulin fibrosisMyeloproliferative neoplasmsMF CD34Recipient miceCytokine assaysMPN patientsBone marrowPro-inflammatory cytokine interleukin-8IL8 expressionElevated pro-inflammatory cytokinesPV/ET patientsAdvisory CommitteeWT recipient miceLarger spleen sizePro-inflammatory cytokinesPro-inflammatory pathwaysBone marrow fibrosisS100A8/A9Hallmark featureCytokine interleukin-8Enhanced surface expression