{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:53:29Z","timestamp":1790902409008,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bcr\u2010abl signals for leukemogenesis of chronic myeloid leukemia (CML) and activates ras. Since the function of promyelocytic leukemia protein (pml) is provoked by ras to promote apoptosis and senescence in untransformed cells, the function is probably masked in CML. Imatinib specifically inhibits bcr\u2010abl and induces apoptosis of CML cells. As reported previously, p53<jats:sup>wild<\/jats:sup> CML was more resistant to imatinib than that lacking p53. Here, we searched for an imatinib\u2010induced p53 independent proapoptotic mechanism. We found imatinib up\u2010regulated phosphorylation of p38 mitogen\u2010activated protein kinase (MAPK), checkpoint kinase 2 (chk2) and transactivation\u2010competent (TA) p73; expression of pml and bax; formation of PML\u2010nuclear body (NB); and co\u2010localization of TAp73\/PML\u2010NB in p53\u2010nonfunctioning K562 and p53<jats:sup>mutant<\/jats:sup> Meg\u201001 CML cells, but not in <jats:italic>BCR\u2010ABL<\/jats:italic><jats:sup>\u2010<\/jats:sup> HL60 cells. In K562 cells, with short interfering RNAs (siRNAs), knockdown of pml led to dephosphorylation of TAp73. Knockdown of either pml or TAp73 abolished the imatinib\u2010induced apoptosis. Inhibition of p38 MAPK with SB203580 led to dephosphorylation of TAp73, abolishment of TAp73\/PML\u2010NB co\u2010localization, and the subsequent apoptosis. Conversely, interferon \u03b1\u20102a (IFN\u03b1), which increased phosphrylated TAp73 and TAp73\/PML\u2010NB co\u2010localization, increased additively apoptosis with imatinib. The imatinib\u2010induced TAp73\/PML\u2010NB co\u2010localization was accompanied by co\u2010immpunoprecipitation of TAp73 with pml. The imatinib\u2010induced co\u2010localization was also found in primary CML cells from 3 of 6 patients, including 2 with p53<jats:sup>mutant<\/jats:sup> and one with p53<jats:sup>wild<\/jats:sup>. A novel p53\u2010independent proapoptotic mechanism using p38 MAPK \/pml\/TAp73 axis with a step processing at PML\u2010NB and probably with chk2 and bax being involved is hereby evident in some imatinib\u2010treated CML cells. \u00a9 2009 UICC<\/jats:p>","DOI":"10.1002\/ijc.24329","type":"journal-article","created":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T14:38:38Z","timestamp":1233671918000},"page":"71-77","source":"Crossref","is-referenced-by-count":7,"title":["Pml and TAp73 interacting at nuclear body mediate imatinib\u2010induced p53\u2010independent apoptosis of chronic myeloid leukemia cells"],"prefix":"10.1002","volume":"125","author":[{"given":"Jin\u2010Hwang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin\u2010Cheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chueh\u2010Chuan","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyh\u2010Pyng","family":"Gau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Shu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Hwai","family":"Tzeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,3,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0596-561"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402940"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.3.9.1126"},{"key":"e_1_2_6_5_2","first-page":"337","article-title":"p53 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