Show simple item record

dc.contributor.authorRichartz, N
dc.contributor.authorDuthil, E
dc.contributor.authorFord, A
dc.contributor.authorNaderi, EH
dc.contributor.authorBhagwat, S
dc.contributor.authorGilljam, KM
dc.contributor.authorBurman, MM
dc.contributor.authorRuud, E
dc.contributor.authorBlomhoff, HK
dc.contributor.authorSkah, S
dc.date.accessioned2019-12-13T13:39:16Z
dc.date.issued2019-11
dc.identifier.citationBlood advances, 2019, 3 (21), pp. 3181 - 3190
dc.identifier.issn2473-9529
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3466
dc.identifier.eissn2473-9537
dc.identifier.doi10.1182/bloodadvances.2019000473
dc.description.abstractAcute lymphoblastic leukemia (ALL) develops in the bone marrow in the vicinity of stromal cells known to promote tumor development and treatment resistance. We previously showed that the cyclooxygenase (COX) inhibitor indomethacin prevents the ability of stromal cells to diminish p53-mediated killing of cocultured ALL cells in vitro, possibly by blocking the production of prostaglandin E2 (PGE2). Here, we propose that PGE2 released by bone marrow stromal cells might be a target for improved treatment of pediatric ALL. We used a xenograft model of human primary ALL cells in nonobese diabetic-scid IL2rγnull mice to show that indomethacin delivered in the drinking water delayed the progression of ALL in vivo. The progression was monitored by noninvasive in vivo imaging of the engrafted leukemic cells, as well as by analyses of CD19+CD10+ leukemic blasts present in spleen or bone marrow at the termination of the experiments. The indomethacin treatment increased the level of p53 in the leukemic cells, implying that COX inhibition might reduce progression of ALL by attenuating protective paracrine PGE2 signaling from bone marrow stroma to leukemic cells.
dc.formatPrint
dc.format.extent3181 - 3190
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectTumor Cells, Cultured
dc.subjectBone Marrow
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectDisease Models, Animal
dc.subjectDisease Progression
dc.subjectIndomethacin
dc.subjectDinoprostone
dc.subjectCyclooxygenase Inhibitors
dc.subjectXenograft Model Antitumor Assays
dc.subjectImmunophenotyping
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectMale
dc.subjectProstaglandin-Endoperoxide Synthases
dc.subjectTumor Suppressor Protein p53
dc.subjectPrecursor Cell Lymphoblastic Leukemia-Lymphoma
dc.subjectBiomarkers
dc.titleTargeting cyclooxygenase by indomethacin decelerates progression of acute lymphoblastic leukemia in a xenograft model.
dc.typeJournal Article
dcterms.dateAccepted2019-09-05
rioxxterms.versionofrecord10.1182/bloodadvances.2019000473
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBlood advances
pubs.issue21
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.publication-statusPublished
pubs.volume3
pubs.embargo.termsNo embargo
icr.researchteamBiology of Childhood Leukaemiaen_US
dc.contributor.icrauthorFord, Anthonyen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0