Evaluation of CD160 and CD200 Expression as Differentiating Markers between Chronic Lymphocytic Leukemia and Other Mature B-Cell Neoplasms
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Abstract
Background: The present work aimed to investigate the expression of CD160/ CD200 in CLL and other mature B-cell neoplasms (MBN) and their use as an additional diagnostic tool for differentiating CLL from other MBN.
Materials and Methods: Using flowcytometry, we detected the expression of CD160 &CD200 on B-cells from 30 CLL patients, 30 other MBN patients in addition to 20 controls. CDs160/200 measurements were determined as a percentage expression (≥20% was considered positive) and as a ratio of the mean fluorescence intensities (MFIR) of leukemic cells/controls and were considered positive when the ratios were ≥2 and 20, respectively.
Results: 90% and 100% of the CLL group expressed CDs160/200 in comparison to 60% and 63.3% of other MBN (p=0.007, p<0.001) respectively. By MFIR; 96.7% and 50% of our CLL group expressed CDs160/200 in comparison to 76.7% and 30% of other MBN, respectively. CDs160/ 200 were not expressed on the controls. Positive co-expression of CD160 and CD200 was found in 90% of the CLL cases, 60% of HCL patients & only in 40% of B-NHL. However, double negative expression of both markers was found only in 24% of the B-NHL patients.
Conclusion: CD160 with CD200 can be used as additional diagnostic markers to the available routine panel to differentiate between B-CLL & other non-specified B-NHL patients.
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1. Zwiebel JA, Cheson BD. Chronic lymphocytic leukemia: staging and prognostic factors. Semin Oncol. 1998; 25(1): 42-59.
2. Zent CS, Kyasa MJ, Evans R, et al. Chronic lymphocytic leukemia incidence is substantially higher than estimated from tumor registry data. Cancer. 2001; 92(5):1325–30.
3. Dronca RS, Jevremovic D, Hanson CA, et al. CD5-positive chronic B-cell lymphoproliferative disorders: Diagnosis and prognosis of a heterogeneous disease entity. Cytometry B Clin Cytom. 2010; 78(Suppl 1): S35–S41.
4. Matutes E, Owusu-Ankomah K, Morilla R, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia. 1994; 8(10): 1640–5.
5. Moreau EJ, Matutes E, A’Hern RP, et al. Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b). Am J Clin Pathol. 1997; 108(4):378–82.
6. Maloum K, Davi F, Magnac C, et al. Analysis of VH gene expression in CD5+ and CD5- B-cell chronic lymphocytic leukemia. Blood. 1995; 86(10):3883–90.
7. Maïza H, Leca G, Mansur IG, et al. A novel 80-kD cell surface structure identifies human circulating lymphocytes with natural killer activity. J Exp Med. 1993; 178(3): 1121-1126.
8. Bensussan A, Rabian C, Schiavon V, et al. Significant enlargement of a specific subset of CD3+CD8+ peripheral blood leukocytes mediating cytotoxic T-lymphocyte activity during human immunodeficiency virus infection. Proc Natl Acad Sci USA. 1993; 90(20): 9427-9430.
9. Schmitt C, Ghazi B, Bellier F, et al. Identification and analysis of the human CD160 promoter: implication of a potentialAML-1 binding site in promoter activation. Genes Immun. 2009; 10(7):616-23.
10. Agrawal S, Marquet J, Freeman GJ, et al. Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells. J Immunol. 1999; 162(3):1223–6.
11. Bouteiller Le, Barakonyi A, Giustiniani J, et al. Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity. Proc Natl Acad Sci USA. 2002; 99(26):16963–8.
12. Barakonyi A, Rabot M, Marie-Cardine A, et al. Cutting edge: engagement of CD160 by its HLA-C physiological ligand triggers a unique cytokine profile secretion in the cytotoxic peripheral blood NK cell subset. J Immunol. 2004; 173(9):5349–54.
13. Tsujimura K, Obata Y, Matsudaira Y, et al. Characterization of murine CD160+ CD8+ T lymphocytes. Immuno lLett. 2006; 106(1):48–56.
14. Liu FT, Giustiniani J, Farren T, et al. CD160 signaling mediates PI3K-dependent survival and growth signals in chronic lymphocytic leukemia. Blood. 2010; 115(15): 3079-88.
15. Barclay AN, Wright GJ, Brooke G, et al. CD 200 and membrane protein interactions in the control of myeloid cells. Trends Immunol. 2002; 23(6):285-90.
16. Lesesve JF, Tardy S, Frotscher B, et al. Combination of CD160 and CD200 as a useful tool for differential diagnosis between chronic lymphocytic leukemia and other mature B-cell neoplasms. Int J Lab Hematol. 2015; 37(4):486-94.
17. McCaughan GW, Clark MJ, Barclay AN. Characterization of the human homologue of the rat MRC OX-2 membrane glycoprotein. Immunogenetics. 1987; 25(5):329-35.
18. McCaughan GW, Clark MJ, Hurst J, et al. The gene for MRC OX-2 membrane glycoprotein is localized on human chromosome 3. Immunogenetics. 1987; 25(2):133-5.
19. Minas K, Liversidge J. Is the CD200/CD200receptor interaction more than just a myeloid cell inhibitory signal?. Crit Rev Immunol. 2006; 26(3):213-30.
20. EL Desoukey NA, Afify RA, Amin DG, et al. CD200 Expression in B-Cell Chronic Lymphoproliferative Disorders. J Investig Med. 2012; 60(1): 56-61.
21. Farren TW, Giustiniani J, Liu FT, et al. Differential and tumor-specific expression of CD160 in B-cell malignancies. Blood. 2011; 118(8): 2174–83.
22. Alapat D, Coviello-Malle J, Owens R, et al. Diagnostic usefulness and prognostic impact of CD200 expression in lymphoid malignancies and plasma cell myeloma. Am J Clin Pathol. 2012; 137(1): 93–100.
23. Zhang ZH, Chen S, Liu Y, et al. High levels of CD160 expression up-regulated counts of chronic lymphocytic leukemia cells and were associated with other clinical parameters in Chinese patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2015; 56(2):529–32.
24. Spacek M, Karban J, Radek M, et al. CD200 expression improves differential diagnosis between chronic lymphocytic leukemia and mantle cell lymphoma. Blood. 2014; 124(21):5637.
25. Gorczynski RM. Role for expression of CD200 in multiparameter flow cytometric differential diagnosis of mature B-cell neoplasms. J Lab Precis Med. 2017; 2(8):57.
26. Poongodi R, Varma N, Naseem S, et al. Utility of CD200 Expression and CD20 Antibody Binding Capacity in Differentiating Chronic Lymphocytic
1. Zwiebel JA, Cheson BD. Chronic lymphocytic leukemia: staging and prognostic factors. Semin Oncol. 1998; 25(1): 42-59.
2. Zent CS, Kyasa MJ, Evans R, et al. Chronic lymphocytic leukemia incidence is substantially higher than estimated from tumor registry data. Cancer. 2001; 92(5):1325–30.
3. Dronca RS, Jevremovic D, Hanson CA, et al. CD5-positive chronic B-cell lymphoproliferative disorders: Diagnosis and prognosis of a heterogeneous disease entity. Cytometry B Clin Cytom. 2010; 78(Suppl 1): S35–S41.
4. Matutes E, Owusu-Ankomah K, Morilla R, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia. 1994; 8(10): 1640–5.
5. Moreau EJ, Matutes E, A’Hern RP, et al. Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b). Am J Clin Pathol. 1997; 108(4):378–82.
6. Maloum K, Davi F, Magnac C, et al. Analysis of VH gene expression in CD5+ and CD5- B-cell chronic lymphocytic leukemia. Blood. 1995; 86(10):3883–90.
7. Maïza H, Leca G, Mansur IG, et al. A novel 80-kD cell surface structure identifies human circulating lymphocytes with natural killer activity. J Exp Med. 1993; 178(3): 1121-1126.
8. Bensussan A, Rabian C, Schiavon V, et al. Significant enlargement of a specific subset of CD3+CD8+ peripheral blood leukocytes mediating cytotoxic T-lymphocyte activity during human immunodeficiency virus infection. Proc Natl Acad Sci USA. 1993; 90(20): 9427-9430.
9. Schmitt C, Ghazi B, Bellier F, et al. Identification and analysis of the human CD160 promoter: implication of a potentialAML-1 binding site in promoter activation. Genes Immun. 2009; 10(7):616-23.
10. Agrawal S, Marquet J, Freeman GJ, et al. Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells. J Immunol. 1999; 162(3):1223–6.
11. Bouteiller Le, Barakonyi A, Giustiniani J, et al. Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity. Proc Natl Acad Sci USA. 2002; 99(26):16963–8.
12. Barakonyi A, Rabot M, Marie-Cardine A, et al. Cutting edge: engagement of CD160 by its HLA-C physiological ligand triggers a unique cytokine profile secretion in the cytotoxic peripheral blood NK cell subset. J Immunol. 2004; 173(9):5349–54.
13. Tsujimura K, Obata Y, Matsudaira Y, et al. Characterization of murine CD160+ CD8+ T lymphocytes. Immuno lLett. 2006; 106(1):48–56.
14. Liu FT, Giustiniani J, Farren T, et al. CD160 signaling mediates PI3K-dependent survival and growth signals in chronic lymphocytic leukemia. Blood. 2010; 115(15): 3079-88.
15. Barclay AN, Wright GJ, Brooke G, et al. CD 200 and membrane protein interactions in the control of myeloid cells. Trends Immunol. 2002; 23(6):285-90.
16. Lesesve JF, Tardy S, Frotscher B, et al. Combination of CD160 and CD200 as a useful tool for differential diagnosis between chronic lymphocytic leukemia and other mature B-cell neoplasms. Int J Lab Hematol. 2015; 37(4):486-94.
17. McCaughan GW, Clark MJ, Barclay AN. Characterization of the human homologue of the rat MRC OX-2 membrane glycoprotein. Immunogenetics. 1987; 25(5):329-35.
18. McCaughan GW, Clark MJ, Hurst J, et al. The gene for MRC OX-2 membrane glycoprotein is localized on human chromosome 3. Immunogenetics. 1987; 25(2):133-5.
19. Minas K, Liversidge J. Is the CD200/CD200receptor interaction more than just a myeloid cell inhibitory signal?. Crit Rev Immunol. 2006; 26(3):213-30.
20. EL Desoukey NA, Afify RA, Amin DG, et al. CD200 Expression in B-Cell Chronic Lymphoproliferative Disorders. J Investig Med. 2012; 60(1): 56-61.
21. Farren TW, Giustiniani J, Liu FT, et al. Differential and tumor-specific expression of CD160 in B-cell malignancies. Blood. 2011; 118(8): 2174–83.
22. Alapat D, Coviello-Malle J, Owens R, et al. Diagnostic usefulness and prognostic impact of CD200 expression in lymphoid malignancies and plasma cell myeloma. Am J Clin Pathol. 2012; 137(1): 93–100.
23. Zhang ZH, Chen S, Liu Y, et al. High levels of CD160 expression up-regulated counts of chronic lymphocytic leukemia cells and were associated with other clinical parameters in Chinese patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2015; 56(2):529–32.
24. Spacek M, Karban J, Radek M, et al. CD200 expression improves differential diagnosis between chronic lymphocytic leukemia and mantle cell lymphoma. Blood. 2014; 124(21):5637.
25. Gorczynski RM. Role for expression of CD200 in multiparameter flow cytometric differential diagnosis of mature B-cell neoplasms. J Lab Precis Med. 2017; 2(8):57.
26. Poongodi R, Varma N, Naseem S, et al. Utility of CD200 Expression and CD20 Antibody Binding Capacity in Differentiating Chronic Lymphocytic
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| Issue | Vol 14, No 1 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v14i1.2358 | |
| Keywords | ||
| CLL; MBN; CD200; CD160; Flowcytometry | ||
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How to Cite
1.
El- Neanaey W, Swelem R, Ghallab O, Abu-Shelou S. Evaluation of CD160 and CD200 Expression as Differentiating Markers between Chronic Lymphocytic Leukemia and Other Mature B-Cell Neoplasms. Int J Hematol Oncol Stem Cell Res. 2020;14(1):27-37.
