Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 6/2012

01.06.2012 | Original Paper

Quantification of ZAP-70 mRNA by real-time PCR is a prognostic factor in chronic lymphocytic leukemia

verfasst von: Yin-Hua Wang, Zhi-Jian Zou, Ling Liu, Li-Na Zhang, Cheng Fang, Dan-Xia Zhu, Lei Fan, Jian-Yong Li, Wei Xu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2012

Einloggen, um Zugang zu erhalten

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.
Literatur
Zurück zum Zitat Antic D, Mihaljevic B, Cokic V, Fekete MD, Djurasevic TK, Pavlovic S et al (2011) Patients with early stage chronic lymphocytic leukemia: new risk stratification based on molecular profiling. Leuk Lymphoma 52(7):1394–1397PubMedCrossRef Antic D, Mihaljevic B, Cokic V, Fekete MD, Djurasevic TK, Pavlovic S et al (2011) Patients with early stage chronic lymphocytic leukemia: new risk stratification based on molecular profiling. Leuk Lymphoma 52(7):1394–1397PubMedCrossRef
Zurück zum Zitat Best OG, Ibbotson RE, Parker AE, Davis ZA, Orchard JA, Oscier DG (2006) ZAP-70 by flow cytometry: a comparison of different antibodies, anticoagulants, and methods of analysis. Cytometry B Clin Cytom 70(4):235–241PubMed Best OG, Ibbotson RE, Parker AE, Davis ZA, Orchard JA, Oscier DG (2006) ZAP-70 by flow cytometry: a comparison of different antibodies, anticoagulants, and methods of analysis. Cytometry B Clin Cytom 70(4):235–241PubMed
Zurück zum Zitat Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J et al (1981) A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48(1):198–206PubMedCrossRef Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J et al (1981) A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48(1):198–206PubMedCrossRef
Zurück zum Zitat Catherwood MA, Matthews C, Niblock R, Dobbin E, Morris TC, Alexander HD (2006) ZAP-70 mRNA quantification in B-cell chronic lymphocytic leukaemia. Eur J Haemato 76(4):294–298CrossRef Catherwood MA, Matthews C, Niblock R, Dobbin E, Morris TC, Alexander HD (2006) ZAP-70 mRNA quantification in B-cell chronic lymphocytic leukaemia. Eur J Haemato 76(4):294–298CrossRef
Zurück zum Zitat Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O’Brien S et al (1996) National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 87(12):4990–4997PubMed Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O’Brien S et al (1996) National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 87(12):4990–4997PubMed
Zurück zum Zitat Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M et al (2003) ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 348(18):1764–1775PubMedCrossRef Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M et al (2003) ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 348(18):1764–1775PubMedCrossRef
Zurück zum Zitat Gibbs G, Bromidge T, Howe D, Hopkins J, Johnson S (2005) Comparison of flow cytometric methods for the measurement of ZAP-70 expression in a routine diagnostic laboratory. Clin Lab Haematol 27(4):258–266PubMedCrossRef Gibbs G, Bromidge T, Howe D, Hopkins J, Johnson S (2005) Comparison of flow cytometric methods for the measurement of ZAP-70 expression in a routine diagnostic laboratory. Clin Lab Haematol 27(4):258–266PubMedCrossRef
Zurück zum Zitat Hamblin T (2002) Chronic lymphocytic leukaemia: one disease or two? Ann Hematol 81(6):299–303PubMedCrossRef Hamblin T (2002) Chronic lymphocytic leukaemia: one disease or two? Ann Hematol 81(6):299–303PubMedCrossRef
Zurück zum Zitat Orchard JA, Ibbotson RE, Davis Z, Wiestner A, Rosenwald A, Thomas PW et al (2004) ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 363(9403):105–111PubMedCrossRef Orchard JA, Ibbotson RE, Davis Z, Wiestner A, Rosenwald A, Thomas PW et al (2004) ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 363(9403):105–111PubMedCrossRef
Zurück zum Zitat Qiu HX, Xu W, Cao XS, Zhou M, Shen YF, Xu YL et al (2008) Cytogenetic characterisation in Chinese patients with chronic lymphocytic leukemia: a prospective, multicenter study on 143 cases analysed with interphase fluorescence in situ hybridisation. Leuk Lymphoma 49(10):1887–1892PubMedCrossRef Qiu HX, Xu W, Cao XS, Zhou M, Shen YF, Xu YL et al (2008) Cytogenetic characterisation in Chinese patients with chronic lymphocytic leukemia: a prospective, multicenter study on 143 cases analysed with interphase fluorescence in situ hybridisation. Leuk Lymphoma 49(10):1887–1892PubMedCrossRef
Zurück zum Zitat Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS (1975) Clinical staging of chronic lymphocytic leukemia. Blood 46(2):219–234PubMed Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS (1975) Clinical staging of chronic lymphocytic leukemia. Blood 46(2):219–234PubMed
Zurück zum Zitat Rassenti LZ, Huynh L, Toy TL, Chen L, Keating MJ, Gribben JG et al (2004) ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 351(9):893–901PubMedCrossRef Rassenti LZ, Huynh L, Toy TL, Chen L, Keating MJ, Gribben JG et al (2004) ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 351(9):893–901PubMedCrossRef
Zurück zum Zitat Rosenwald A, Alizadeh AA, Widhopf G, Simon R, Davis RE, Yu X et al (2001) Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 194(11):1639–1647PubMedCrossRef Rosenwald A, Alizadeh AA, Widhopf G, Simon R, Davis RE, Yu X et al (2001) Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 194(11):1639–1647PubMedCrossRef
Zurück zum Zitat Shankey TV, Forman M, Scibelli P, Cobb J, Smith CM, Mills R et al (2006) An optimized whole blood method for flow cytometric measurement of ZAP-70 protein expression in chronic lymphocytic leukemia. Cytometry B Clin Cytom 70(4):259–269PubMed Shankey TV, Forman M, Scibelli P, Cobb J, Smith CM, Mills R et al (2006) An optimized whole blood method for flow cytometric measurement of ZAP-70 protein expression in chronic lymphocytic leukemia. Cytometry B Clin Cytom 70(4):259–269PubMed
Zurück zum Zitat Sheikholeslami MR, Jilani I, Keating M, Uyeji J, Chen K, Kantarjian H et al (2006) Variations in the detection of ZAP-70 in chronic lymphocytic leukemia: Comparison with IgV(H) mutation analysis. Cytometry B Clin Cytom 70(4):270–275PubMed Sheikholeslami MR, Jilani I, Keating M, Uyeji J, Chen K, Kantarjian H et al (2006) Variations in the detection of ZAP-70 in chronic lymphocytic leukemia: Comparison with IgV(H) mutation analysis. Cytometry B Clin Cytom 70(4):270–275PubMed
Zurück zum Zitat Stamatopoulos B, Meuleman N, Haibe-Kains B, Duvillier H, Massy M, Martiat P et al (2007) Quantification of ZAP70 mRNA in B cells by real-time PCR is a powerful prognostic factor in chronic lymphocytic leukemia. Clin Chem 53(10):1757–1766PubMedCrossRef Stamatopoulos B, Meuleman N, Haibe-Kains B, Duvillier H, Massy M, Martiat P et al (2007) Quantification of ZAP70 mRNA in B cells by real-time PCR is a powerful prognostic factor in chronic lymphocytic leukemia. Clin Chem 53(10):1757–1766PubMedCrossRef
Zurück zum Zitat Tobin G, Rosenquist R (2005) Prognostic usage of V(H) gene mutation status and its surrogate markers and the role of antigen selection in chronic lymphocytic leukemia. Med Oncol 22(3):217–228PubMedCrossRef Tobin G, Rosenquist R (2005) Prognostic usage of V(H) gene mutation status and its surrogate markers and the role of antigen selection in chronic lymphocytic leukemia. Med Oncol 22(3):217–228PubMedCrossRef
Zurück zum Zitat Wang YH, Fan L, Xu W, Li JY (2011) Detection methods of ZAP-70 in chronic lymphocytic leukemia. Clin Exp Med (Epub ahead of print) Wang YH, Fan L, Xu W, Li JY (2011) Detection methods of ZAP-70 in chronic lymphocytic leukemia. Clin Exp Med (Epub ahead of print)
Zurück zum Zitat Xu W, Cao X, Miao KR, Qiao C, Wu YJ, Liu Q et al (2009a) Serum thymidine kinase 1 concentration in Chinese patients with chronic lymphocytic leukemia and its correlation with other prognostic factors. Int J Hematol 90(2):205–211PubMedCrossRef Xu W, Cao X, Miao KR, Qiao C, Wu YJ, Liu Q et al (2009a) Serum thymidine kinase 1 concentration in Chinese patients with chronic lymphocytic leukemia and its correlation with other prognostic factors. Int J Hematol 90(2):205–211PubMedCrossRef
Zurück zum Zitat Xu W, Li JY, Wu YJ, Yu H, Shen QD, Tian T et al (2009b) CD38 as a prognostic factor in Chinese patients with chronic lymphocytic leukaemia. Leuk Res 33(2):237–243PubMedCrossRef Xu W, Li JY, Wu YJ, Yu H, Shen QD, Tian T et al (2009b) CD38 as a prognostic factor in Chinese patients with chronic lymphocytic leukaemia. Leuk Res 33(2):237–243PubMedCrossRef
Zurück zum Zitat Zanotti R, Ambrosetti A, Lestani M, Ghia P, Pattaro C, Remo A et al (2007) ZAP-70 expression, as detected by immunohistochemistry on bone marrow biopsies from early-phase CLL patients, is a strong adverse prognostic factor. Leukemia 21(1):102–109PubMedCrossRef Zanotti R, Ambrosetti A, Lestani M, Ghia P, Pattaro C, Remo A et al (2007) ZAP-70 expression, as detected by immunohistochemistry on bone marrow biopsies from early-phase CLL patients, is a strong adverse prognostic factor. Leukemia 21(1):102–109PubMedCrossRef
Metadaten
Titel
Quantification of ZAP-70 mRNA by real-time PCR is a prognostic factor in chronic lymphocytic leukemia
verfasst von
Yin-Hua Wang
Zhi-Jian Zou
Ling Liu
Li-Na Zhang
Cheng Fang
Dan-Xia Zhu
Lei Fan
Jian-Yong Li
Wei Xu
Publikationsdatum
01.06.2012
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2012
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-012-1177-3

Weitere Artikel der Ausgabe 6/2012

Journal of Cancer Research and Clinical Oncology 6/2012 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.