title: Quantification of ZAP-70 mRNA by real-time PCR is a prognostic factor in chronic lymphocytic leukemia.
abstract: BACKGROUND
  Chronic lymphocytic leukemia (CLL) is heterogeneous with respect to prognosis and clinical outcome. Mutational status of immunoglobulin heavy chain variable region (IGHV) appears to be a particularly strong prognostic marker, but it is difficult to perform in a routine clinical laboratory. ζ-chain-associated protein kinase 70 kDa (ZAP-70) protein detected by flow cytometry is a strong surrogate marker of IGHV mutational status; however, it suffers from the lack of standardization.
  
  
  METHODS
  We investigated whether ZAP-70 mRNA expression level can be a prognostic factor in CLL. Real-time quantitative polymerase chain reaction was used to analyze ZAP-70 mRNA expression from 102 CLL patients.
  
  
  RESULTS
  The expression of ZAP-70 mRNA was significantly associated with Binet stage (P < 0.001), lactate dehydrogenase (P = 0.003), ZAP-70 protein (P = 0.018), IGHV mutational status (P = 0.038), and cytogenetic abnormality of del(17p13) or del(11q22.3) (P = 0.037) in CLL patients. According to receiver operating characteristic curve analysis for ZAP-70 mRNA and ZAP-70 protein, positive ZAP-70 mRNA (P = 0.006) was an adverse factor in determining the treatment free survival (TFS). In a multivariate Cox analysis of TFS, ZAP-70 mRNA is not ideal as an independent prognostic factor. However, ZAP-70 mRNA was statistically significant in predicting treatment response.
  
  
  CONCLUSIONS
  This study demonstrated the value of determination of ZAP-70 mRNA in providing useful prognostic information in CLL patients. However, ZAP-70 mRNA is not an independent prognostic factor.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
authors.forename: Yin-Hua
authors.initials: YH
authors.lastname: Wang
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Zou
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Fang
authors.forename: Dan-Xia
authors.initials: DX
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D007770:L-Lactate Dehydrogenase; D051746:ZAP-70 Protein-Tyrosine Kinase