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Rocca, B. et al.

Rocca, Morosetti, Habib, Maggiano, Zassadowski, Ciabattoni, Chomienne, Papp, Ranelletti,

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

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 PGE(2) 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.Leukemia (2004) 18, 1373-1379. doi:10.1038/sj.leu.2403407 Published online 10 June 2004[1]

References

Cyclooxygenase-1, but not -2, is upregulated in NB4 leukemic cells and human primary promyelocytic blasts during differentiation. Rocca, B., Morosetti, R., Habib, A., Maggiano, N., Zassadowski, F., Ciabattoni, G., Chomienne, C., Papp, B., Ranelletti, F.O. Leukemia (2004) [Pubmed]

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