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ZAP-70 Protein Expression in B-cell Chronic Lymphoid Leukemia: a Single Center Experience from Pakistan

  • Zeeshan, Rozina (Department of Hematology, Liaquat National Hospital) ;
  • Irfan, Syed Mohammed (Department of Hematology, Liaquat National Hospital) ;
  • Sultan, Sadia (Department of Hematology, Liaquat National Hospital) ;
  • Bhimani, Sanjana (Liaquat National Medical College)
  • Published : 2015.03.09

Abstract

Background: Chronic lymphoid leukemia (CLL) is the most frequent type of adult leukemia. The Rai and Binet staging systems have been well recognized as standards for assessing the treatment requirements and overall survival in CLL patients. However, there is a need to seek newer prognostic markers to identify stable or progressive forms of CLL that will facilitate risk-adapted treatment strategies. Currently a molecular biomarker ZAP-70 has attracted interest as providing prognostic information in CLL patients. Objective: To determine the frequency of ZAP-70 positivity in B-CLL patients at disease presentation. Materials and Methods: From January 2011 to September 2014, 89 patients were diagnosed to have chronic lymphoid leukemia. Complete blood count was done on an automated analyzer (Cell Dyne, Abott Architect, USA), while immunophenotyping was conducted for each patient to establish the diagnosis of the disease. ZAP-70 expression was evaluated by flow cytometry. Data were compiled and analyzed by SPSS version 21. Results: Out of the total of 89 B-CLL patients, 62 (69.7%) were male and 27 (30.3%) were females with a male to female ratio of 2:1. The mean age was $57.5{\pm}12.1years$. The frequency of ZAP-70 positivity in our B-CLL patients was found to be 13.5%. ZAP-70 positivity was significantly correlated with stage III disease and high absolute lymphocytic count (P<0.05). No correlation of ZAP-70 could be established with age and gender (p>0.05). Conclusions: The frequency of ZAP-70 in our patients appears low. It is approximately half that in international data. We would recommend to screen all the newly diagnosed patients with CLL for ZAP-70 protein expression for risk stratification, family counseling and to predict overall survival.

Keywords

Chronic lymphoid leukemia;ZAP-70;B-cell;Pakistan

References

  1. Abbott BL (2004). Advances in the diagnosis and treatment of chronic lymphocytic leukemia. Clin Adv Hematol Oncol, 2, 448-54.
  2. Baliakas P, Kanellis G, Stavroyianni N, et al (2013). The role of bone marrow biopsy examination at diagnosis of chronic lymphocytic leukemia: a reappraisal. Leuk Lymphoma, 54, 2377-84. https://doi.org/10.3109/10428194.2013.780653
  3. D'Arena G, Tarnani M, Rumi C, et al (2007). Prognostic significance of combined analysis of ZAP-70 and CD38 in chronic lymphocytic leukemia. Am J Hematol, 82, 787-91. https://doi.org/10.1002/ajh.20936
  4. Del Principe MI, Del Poeta G, Buccisano F, et al (2006). Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood, 108, 853-61. https://doi.org/10.1182/blood-2005-12-4986
  5. Dodhy MA, Zafar H, Aslam W (2011). Chronic lymphocytic leukemia: an experience of a decade at a tertiary care hospital. Ann Pak Inst Med Sci, 7, 196-9.
  6. Dohner H, Fischer K, Bentz M, et al (1995). p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood, 85, 580-9.
  7. El- Sharnouby JA, el-Shakankiri AA, Hendy OM, Ahmed LM, Taha AM (2006). Egypt J Immunol, 13, 69-84.
  8. Gogia A, Sharma A, Raina V, et al (2013). Prevalence of ZAP-70 and CD38 in Indian chronic lymphocytic leukemia patients. Indian J Cancer, 50, 333-6. https://doi.org/10.4103/0019-509X.123620
  9. Gribben JG (2008). Molecular profiling in CLL. Hematology Am Soc Hematol Educ Program, 2008, 444-9. https://doi.org/10.1182/asheducation-2008.1.444
  10. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK (1999). Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood, 94, 1848-54.
  11. Hallek M, Langenmayer I, Nerl C, et al (1999). Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia. Blood, 93, 1732-7.
  12. Junaid A, Rao PN, Adil MM (2011). Chromosomal study for prognostic grouping in chronic lymphocytic leukemia. J Coll Physicians Surg Pak, 21, 19-22.
  13. Kermani IA, Dehdilani M, Dolatkhah R (2007). Chronic lymphocytic leukemia in the recent 10 years and treatment effects of fludarabin. Asian Pacific J Cancer Prev, 8, 367-71.
  14. Khan M, Saif A, Sandler S, Mirrakhimov AE (2014). Idelalisib for the treatment of chronic lymphocytic leukemia. ISRN Oncol, 2014, 931858.
  15. Li ZJ, Qiu LG, Wu T, et al (2008). The clinical and laboratory features of 263 cases of chronic lymphocytic leukemia. Zhonghua Xue Ye Xue Za Zhi, 29, 300-3.
  16. Crespo M, Bosch F, Villamor N, et al (2003). ZAP-70 Expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med, 348, 1764-75. https://doi.org/10.1056/NEJMoa023143
  17. Marti GE, Carter P, Abbasi F, et al (2003). B-cell monoclonal lymphocytosis and B-cell abnormalities in the setting of familial B-cell chronic lymphocytic leukemia. Cytometry B Clin Cytom, 52, 1-12.
  18. Hallek M, Cheson BD, Catovsky D, et al (2008). A report from the international workshop on chronic lymphocytic leukemia updating the national cancer institute working group 1996 guidelines: Blood, 111, 5446-56 https://doi.org/10.1182/blood-2007-06-093906
  19. Moreno C, Montserrat E (2008). New prognostic markers in chronic lymphocytic leukemia. Blood Rev, 22, 211-9. https://doi.org/10.1016/j.blre.2008.03.003
  20. Mozaheb Z, Hasanzadeh NazarAbadi MH, Aghaee MA (2012). Chronic lymphocytic leukemia and prognostic factors. Asian Pacific J Cancer Prev, 13, 3009-13. https://doi.org/10.7314/APJCP.2012.13.7.3009
  21. Chiorazzi N, Rai KR, Ferrarini M (2005). Chronic lymphocytic leukemia. N Engl J Med, 352, 804-815 https://doi.org/10.1056/NEJMra041720
  22. Qi RJ, Zhang PH, Qiu LG, et al (2009). Clinical significance of ZAP-70 protein expression in chronic lymphocytic leukemia/ small lymphocytic lymphoma. Zhonghua Bing Li Xue Za Zhi, 38, 329-32.
  23. Rassenti LZ, Huynh L, Toy TL, 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, 893-901. https://doi.org/10.1056/NEJMoa040857
  24. Rafiq N, Iqbal T, Shahid M, Muhammad F (2014). Hematological and biochemical parameters in Pakistani chronic lymphoblastic leukemia patients. Pak J life Soc Sci, 12, 16-19.
  25. Seiffert M, Schulz A, Ohl S, et al (2010). Soluble CD14 is a novel monocyte derived survival factor for chronic lymphocytic leukemia cells, which is induced by CLL cells in vitro and present at abnormally high levels in vivo. Blood, 116, 4223-30. https://doi.org/10.1182/blood-2010-05-284505
  26. Shanafelt TD (2009). Predicting clinical outcome in CLL. how and why. Hematology Am Soc Hematol Educ Program, 2009, 421-9. https://doi.org/10.1182/asheducation-2009.1.421
  27. Sagatys EM, Zhang L (2012). Clinical and laboratory prognostic indicators in chronic lymphocytic leukemia. Cancer Control, 19, 18-25. https://doi.org/10.1177/107327481201900103
  28. Siegel R, Ma J, Zou Z, Jemal A (2014). Cancer statistics, 2014 CA Cancer J Clin, 64, 9-29.
  29. Vroblova V, Smolej L, Vrbacky F, et al (2009). Biological prognostic markers in chronic lymphocytic leukemia. Acta Medica Hradec Kralove, 52, 3-8 https://doi.org/10.14712/18059694.2016.99
  30. Wang YH, FanL, Xu W, LiJY (2012). Detection methods of ZAP-70 in chronic lymphocytic leukemia. Clin Exp Med, 12, 69-77. https://doi.org/10.1007/s10238-011-0148-3

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