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.

CONCLUSION:

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: Yin-Hua Wang, Zhi-Jian Zou, Ling Liu, Li-Na Zhang, Cheng Fang, Dan-Xia Zhu, Lei Fan, Jian-Yong Li, Wei Xu
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 138 Issue 6 Pg. 1011-7 (Jun 2012) ISSN: 1432-1335 [Electronic] Germany
• PMID: 22362302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region
• RNA, Messenger
• L-Lactate Dehydrogenase
• ZAP-70 Protein-Tyrosine Kinase

Topics

• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Female
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin Variable Region (genetics)
• L-Lactate Dehydrogenase (genetics)
• Leukemia, Lymphocytic, Chronic, B-Cell (enzymology, genetics, immunology)
• Male
• Middle Aged
• Mutation (genetics)
• Prognosis
• Proportional Hazards Models
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction (methods)
• ZAP-70 Protein-Tyrosine Kinase (genetics)