title: Correlation of seven biological factors (Hsp90a, p53, MDM2, Bcl-2, Bax, Cytochrome C, and Cleaved caspase3) with clinical outcomes of ALK+ anaplastic large-cell lymphoma.
abstract: OBJECTIVE
  To explore correlation of seven apoptosis-related proteins (Hsp90a, p53, MDM2, Bcl-2, Bax, Cytochrome C, and Cleaved caspase3) with clinical outcomes of ALK+ anaplastic large-cell lymphoma (ALCL).
  
  
  METHODS
  Using immunohistochemistry and immunofluorescence double staining methods, the expressions of these seven apoptosis-associated proteins were studied to clarify their relationship with clinical outcomes of 36 ALK+ and 25 ALK-systemic ALCL patients enrolled between 1996 and 2006. The relationship of these apoptosis-regulating proteins with NPM-ALK status was also evaluated with the tyrosine inhibitor herbimycin A (HA) in vitro by immunocytochemistry, Western blotting and flow cytometric assays.
  
  
  RESULTS
  The presence of Hsp90α-, MDM2-, Bax-, Cytochrome C, and Cleaved caspase3-positive tumor cells was found significantly different in ALK+ and ALK-ALCLs, which was correlated with highly favorable clinical outcome. The Bcl-2- and p53-positive tumor cells were found in groups of patients with unfavorable prognosis. Inhibition of NPM-ALK by HA could reactivate the p53 protein and subsequent apoptosis-related proteins and therefore induced apoptosis in ALK+ ALCL cells.
  
  
  CONCLUSIONS
  Our results suggest that these seven proteins might be involved in apoptosis regulation and associated with clinical outcome of ALK+ systemic ALCLs. We also reveal a dynamic chain relation that NPM-ALK regulates p53 expression and subsequent apoptosis cascade in ALK+ ALCLs.
authors.affiliation: Department of Pathology, Nanfang Hospital affiliated to Southern Medical University, Guangzhou 510515 Guangdong, China.
authors.forename: Hui Ling
authors.initials: HL
authors.lastname: Li
authors.forename: Xue Ping
authors.initials: XP
authors.lastname: Huang
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Zhou
authors.forename: Tian Hai
authors.initials: TH
authors.lastname: Ji
authors.forename: Zi Qing
authors.initials: ZQ
authors.lastname: Wu
authors.forename: Zhi Qiang
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Hui Yong
authors.initials: HY
authors.lastname: Jiang
authors.forename: Fan Rong
authors.initials: FR
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D016227:Benzoquinones / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012189:Retrospective Studies; D017828:Rifabutin / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D016227:Benzoquinones; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D017828:Rifabutin; C020754:herbimycin; C107023:p80(NPM-ALK) protein; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases