Investigators at Addenbrooke's Hospital release new data on lymphoma
2009 JUL 13 - (NewsRx.com) -- "Anaplastic large cell lymphoma (ALCL) is characterized by the presence of the t(2;5)(p23;q35) generating the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) fusion protein, a hyperactive kinase with transforming properties. Among these properties is the ability to regulate activity of the p53 tumor suppressor protein," scientists writing in the journal Blood report. "In many human cancers, p53 is inactivated by mutation or other means, in some cases as a result of up-regulation of the negative regulator MDM2. However, the majority of ALK-expressing ALCL carry wild-type p53 and do not over express MDM2. We demonstrate a novel p53-dependent pathogenetic mechanism in ALK-expressing lymphoma. We confirm previously published reports of NPMALK-induced activation of the phosphoinositide (PI) 3-kinase and Jun N-terminal kinase (JNK) stress-activated protein (SAP) kinase proteins, but in this study demonstrate a role for these in the regulation of p53 activity in an intricate signaling system. Specifically, constitutive ALK signaling leads to the functional inactivation and/or degradation of p53 in JNK and MDM2 dependent manners. We also show nuclear exclusion of p53 in a PI 3-kinase-dependent manner," wrote Y.X. Cui and colleagues, Addenbrooke's Hospital. The researchers concluded: "Furthermore, we demonstrate that reactivation of p53 in ALK-expressing cells as a result of pharmacologic inhibition of JNK, PI 3-kinase, and/or MDM2 activities results in the induction of apoptosis suggesting a novel therapeutic modality. (Blood. 2009; 113:5217-5227)." Cui and colleagues published their study in Blood (NPM-ALK inhibits the p53 tumor suppressor pathway in an MDM2 and JNK-dependent manner. Blood, 2009;113(21):5217-5227). Additional information can be obtained by contacting S.D. Turner, Addenbrookes Hospital, Dept. of Pathology, Division Molecular Histopathol, Laboratory Block Level 3, Box 231, Hills Rd., Cambridge CB2 0QQ, UK. The publisher of the journal Blood can be contacted at: American Society Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA. Keywords: United Kingdom, Cambridge, Cancer, Enzyme Research, Hematology, Kinase, Large Cell Lymphoma, Large-Cell Lymphoma, Oncology, Proteomics. Fusion Proteins, Tumor Suppression, Addenbrooke's Hospital. This article was prepared by Proteomics Weekly editors from staff and other reports. Copyright 2009, Proteomics Weekly via NewsRx.com.
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