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Blood Adv. 2019 Nov 12;3(21):3181-3190. doi: 10.1182/bloodadvances.2019000473.

Targeting cyclooxygenase by indomethacin decelerates progression of acute lymphoblastic leukemia in a xenograft model.

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Department of Molecular Medicine, Institute of Basic Medicine, University of Oslo, Oslo, Norway.
Centre for Evolution & Cancer, The Institute of Cancer Research, London, United Kingdom.
Section of Head and Neck Oncology, Department of Oncology, Oslo University Hospital, Oslo, Norway.
Department of Hematology and Oncology, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; and.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.


Acute 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.

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