{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:27:13Z","timestamp":1776144433520,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,7,17]],"date-time":"2008-07-17T00:00:00Z","timestamp":1216252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute promyelocytic leukemia (APL) cells are characterized by PML\/RAR\u03b1 fusion protein, high responsiveness to arsenic trioxide (ATO)\u2010induced cytotoxicity and an abundant generation of reactive oxygen species (ROS). In this study we investigated the association among these three features in APL\u2010derived NB4 cells. We found that NADPH oxidase\u2010derived ROS generation was more abundant in NB4 cells compared with monocytic leukemia U937 cells. By using PR9, a sub\u2010line of U937 stably transduced with the inducible PML\/RAR\u03b1 expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML\/RAR\u03b1 fusion protein, since PML\/RAR\u03b1\u2010expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. On the other hand, the basal intensity of cAMP signaling pathway was compared between NB4 and U937 as well as between PR9 cells with or without PML\/RAR\u03b1, demonstrating that PML\/RAR\u03b1\u2010expressing cells had an impaired cAMP signaling pathway which relieved its inhibitory effect on NADPH oxidase derived ROS generation. In summary, the present study demonstrated the correlation of PML\/RAR\u03b1 with cAMP signaling pathway, NADPH oxidase and ROS generation in APL cells. PML\/RAR\u03b1 that bestows NB4 cells various pathological features, paradoxically also endows these cells with the basis for susceptibility to ATO\u2010induced cytotoxcity. J. Cell. Physiol. 217: 486\u2013493, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21523","type":"journal-article","created":{"date-parts":[[2008,7,17]],"date-time":"2008-07-17T18:13:13Z","timestamp":1216318393000},"page":"486-493","source":"Crossref","is-referenced-by-count":15,"title":["PML\/RAR\u03b1 fusion protein mediates the unique sensitivity to arsenic cytotoxicity in acute promyelocytic leukemia cells: Mechanisms involve the impairment of cAMP signaling and the aberrant regulation of NADPH oxidase"],"prefix":"10.1002","volume":"217","author":[{"given":"Lingna","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard 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