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Cyclooxygenase-1, but not -2, is upregulated in NB4 leukemic cells and human primary promyelocytic blasts during differentiation

Leukemia volume 18, pages 1373–1379 (2004)Cite this article

Abstract

Cyclooxygenase (COX)-1 or -2 and specific prostaglandin (PG) synthases catalyze the formation of various PGs. We investigated the expression and activity of COX-1 and -2 during granulocyte-oriented maturation induced by all-trans-retinoic acid (ATRA) of NB4 cells, originated from a human acute promyelocytic leukemia (APL), and in blasts from APL patients. The expression of COX isoenzymes or prostaglandin synthases was also investigated in circulating granulocytes and human bone marrow. COX-1 was expressed and enzymatically active in NB4 cells and primary blasts. COX-1 mRNA and protein were induced by ATRA. COX-1 protein increased approximately 2–3.5-fold by culture day 3 in NB4 cells and primary blasts, while basal COX-2 expression was very low and unaffected by ATRA. COX-1-dependent PGE2 biosynthesis increased during differentiation approx. 5-fold. Indomethacin and the selective COX-1 inhibitor SC-560, but not selective COX-2 inhibition, impaired NB4 differentiation, reducing NADPH-oxidase activity, CD11b and CD11c expression. The immunohistochemistry of granulocytes and myeloid precursors in the bone marrow showed a large prevalence of COX-1 as compared to COX-2. In conclusion, COX-1 is induced during ATRA-dependent maturation and appears to contribute to myeloid differentiation both in vitro and ex vivo, and COX-1 activity may potentiate the differentiation of human APL.

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Acknowledgements

We are grateful to Professor Carlo Patrono for invaluable suggestions.

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Author notes

  1. B Rocca and R Morosetti: BR and RM contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, Catholic University School of Medicine, Rome, Italy

    B Rocca

  2. Department of Neuroscience, Catholic University School of Medicine, Rome, Italy

    R Morosetti

  3. Department of Biochemistry and Internal Medicine, American University of Beirut, Beirut, Lebanon

    A Habib

  4. Department of Pathology, Catholic University School of Medicine, Rome, Italy

    N Maggiano

  5. Laboratoire de Biologie Cellulaire Hématopoiétique, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France

    F Zassadowski, C Chomienne & B Papp

  6. Department of Drug Sciences, ‘G D'Annunzio’ University of Chieti, Chieti, Italy

    G Ciabattoni

  7. Department of Histology, Catholic University School of Medicine, Rome, Italy

    F O Ranelletti

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  1. B Rocca
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Correspondence to B Rocca.

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This work was supported by grants from the Italian Ministry of University (FIRB Grant N. RBNE01A882_005) (BR) and from the ‘Association pour la Recherche sur le Cancer’ (AH and BP) and the ‘Fondation de France’ (BP).

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Rocca, B., Morosetti, R., Habib, A. et al. Cyclooxygenase-1, but not -2, is upregulated in NB4 leukemic cells and human primary promyelocytic blasts during differentiation. Leukemia 18, 1373–1379 (2004). https://doi.org/10.1038/sj.leu.2403407

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