Title: The significance of CD1d expression in diagnosis of chronic lymphocytic leukemia and its value as a prognostic marker
Authors: Dahlia Ahmed El Sewefy, Gehan Mostafa Hamed
DOI: http://dx.doi.org/10.18535/jmscr/v4i2.56
Back ground Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, its clinical course is highly heterogeneous. Proper diagnosis and discrimination of CLL from other B-chronic lymphoproliferative disorders (B-CLPDs), as well as prediction of disease outcome are very helpful in patient management and therapeutic decision-making. Methods CD1d expression was measured in 43 newly diagnosed B-CLPDs patients including: 20 CLL, 10 MCL and 13 other B-CLPDs, and 10 age- and sex- matched controls. Results Median CD1d % expression in CLL patients (16% [IQR; 9-31]) was significantly lower than normal controls and B-CLPDs (p<0.001). CD1d cut off value <38% can differentiate CLL from MCL and other B-CLPDs with high sensitivity and specificity. CD1d expression was significantly higher in CLL patients with advanced Rai stages (p<0.001), high CD38 expression (31 [20-35] versus, 9 [7.5=12]; p<0.001), poor cytogenetic abnormalities compared with CLL patients without poor cytogenetic abnormalities (15 [8.2 - 32 ] versus, 7.3 [2 - 16.6]; p=0.038). Conclusion CD1d is a useful diagnostic marker that can differentiate CLL from MCL and other B-CLPDs. Higher CD1d expression in CLL is associated with poor prognosis and can define a subpopulation with more aggressive disease. Key words CD1d, CLL, Diagnosis, prognostic marker. 1. Dronca RS, Jevremovic D, Hanson CA, Rabe KG, Shanafelt TD, Morice WG, Call TG, Kay NE, Collins CS, Schwager SM, Slager SL, Zent CS. CD5-positive chronic B-cell lymphoproliferative disorders Diagnosis and prognosis of a heterogeneous disease entity. Cytometry B Clin Cytom. 2010;78: s35–s41. 2. Zent CS, Kyasa MJ, Evans R, Schichman SA. Chronic lymphocytic leukemia incidence is substantially higher than estimated from tumor registry data. Cancer 2001; 92:1325–1330. 3. Rawstron AC, Bennett FL, Connor SJM, Kwok M, Fenoton JAL, Plummer M, De Tute R, Owen RG, Richards SJ, Jack AS, Hillmen P. Monoclonal B-cell lymphocytosis and chronic lymphocitic Leukemia. N Engl J Med. 2008;359:575-83. 4. Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Edu Program 2009;2009:523-531. 5. Costa ES, Pedreira CE, Barrena S, Lecrevisse Q, Flores J, Quijano S, Almeida J, del Carmen García-Macias M, Bottcher S, Van Dongen JJ, Orfao A. Automated pattern-guided principal component analysis vs expert based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping. Leukemia. 2010;24:1927-1933. 6. Morice WG, Kurtin PJ, Hodnefield JM, Shanafelt TD, Hoyer JD, Remstein ED, Hanson CA. Predictive value of blood and bone marrow flow cytometry in B-cell lymphoma classification: comparative analysis of flow cytometry and tissue biopsy in 252 patients. Mayo Clin Proc. 2008;83:776-785. 7. Ho AK, Hill S, Preobrazhensky SN, Miller ME, Chen Z, Bahler DW. Small B-cell neoplasms with typical mantle cell lymphoma immunophenotypes often includes chronic lymphocytic leukemias. Am J Clin Pathol. 2009;131:27-32. 8. Chiorazzi N. Implications of new prognostic markers in chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2012; 2012:76–87. 9. Cornet E, Debliquis A, Rimelen V, Civic N, Docquier M, Troussard X, Drénou B, Matthes T. Developing Molecular Signatures for Chronic Lymphocytic Leukemia. PLoS ONE 2015;10(6): e0128990. doi:10.1371/ journal.pone.0128990. 10. Liu W, Huber SA. Cross talking between CD 1d restricted NKT cells and Y∂ cells in T regulatory cell response. Virology jornal.2011;8:32-40. 11. Metelitsa LS. Anti-tumor potential of type-I NKT cells against CD1d-positiveand CD1d-negative tumors in humans. Clin Immunol. 2011;140:119–29. 12. Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood 1975;46:219–34. 13. Kotsianidis I, Nakou E, Spanoudakis E, Bouchliou I, Moustakidis E, Miltiades P, Vadikolia CM, Szydlo R, Karadimitris A, Tsatalas C. The diagnostic value of CD1d expression in a large cohort of patients withB-cell chronic lymphoproliferative disorders. Am J Clin Pathol 2011;136:400–408. 14. Bojarska-Junak A, Hus I, Chocholska S, Tomczak W, Wos J, Czubak P, Putowski L, Rolinski J. CD1d expression is Higher in chronic lymphocytic leukemia patients with unfavorable prognosis. Leuk Res 2014;38: 435-442. 15. Zheng Z, Venkatapathy S, Rao G. Expression profiling of B cell chronic lymphocytic leukemia suggests deficien CD1-mediated immunity, polarized cytokine response, altere adhesion and increased intracellular protein transport and processing of leukemic cells. Leukemia.2002;16:2429-2437. 16. Chen QY, Zhang T, Pincus SH, Wu S, Ricks D, Liu D, Sun Z, Maclaren N, Lan MS. Human CD1D gene expression is regulated by LEF-1 through distal promoter regulatory elements. J Immunol 2010;184:5047–54. 17. Erdfelder F, Hertweck M, Filipovich A, Uhrmacher S, Kreuzer KA. High lymphoidenhancer-binding factor-1 expression is associated with disease progression and poor prognosis in chronic lymphocytic leukemia. Hematol Rep 2010;2:e3. 18. Gutierrez Jr A, Tschumper RC, Wu X, Shanafelt TD, Eckel-Passow J, Huddleston 3rd PM, Slager SL, Kay NE, Jelinek DF. LEF-1 is a prosurvival factor in chronic lymphocytic leukemiaand is expressed in the preleukemic state of monoclonal B-cell lymphocytosis. Blood 2010;116:2975–83. 19. Howe D, Bromidge T. Variation of LEF-1 mRNA expression in low-grade B-cel lnon-Hodgkin’s lymphoma. Leuk Res 2006;30:29–32. 20. Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL, Buchbinder A, Budman D, Dittmar K, Kolitz J, Lichtman SM, Schulman P, Vinciguerra VP, Rai KR, Ferrarini M, Chiorazzi N. IgV gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999;94:1840-1847. 21. Rassenti LZ, Jain S, Keating MJ, Wierda WG, Grever MR, Byrd JC, Kay NE, Brown JR, Gribben JG, Neuberg DS, He F, Greaves AW, Rai KR, Kipps TJ. Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia. Blood 2008;112:192 –1930 . 22. Hallek M, Pflug N. State of the art treatment of chronic lymphocytic leukemia. Blood 2011;25:1-9. 23. Morabito F, Cutrona G, Gentile M, Matis S, Todoerti K, Colombo M, Sonaglio C, Fabris S, Reverberi D, Megna M, Spriano M, Lucia E, Rossi E, Callea V, Mazzone C, Festini G, Zupo S, Molica S, Neri A, Ferrarini M. Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia. Br J Haematol 2009;146:44 – 53. 24. Anastasiadis A, Kontsianidis I, Papadopoulos V, Spanoudakis E, Margaritis D, Christoforidou A, Gouliamtzi S, Tsatalas C. CD1d expression as a prognostic marker for chronic lymphocytic leukemia. Leuk Lymphoma 2014;55:320-325. 25. Jadidi-Niaragh F, Tehrani M, Ansaripour B, Razavi SM, Sharifian RA, Shokri F. Reduced frequency of NKTT- like cells in patients with progressive chronic lymphocytic leukemia. Med Oncol 2012;29:3561-3569.Abstract
References