Title: Possible Applications of Nucleotidases in B-Chronic Lymphocytic Leukemia Patients; Egyptian Single Centre Study
Authors: Youssef SR, Farweez BA, Salah Al-din YM, Ayoub MS
DOI: http://dx.doi.org/10.18535/jmscr/v3i10.32
The high variability of chronic lymphocytic leukemia (CLL) clinical presentation and disease course has been linked to availability of extracellular nucleotides and nucleosides under control of enzymes as CD39 and CD73. In this work we aimed to study the relation of CD39 and CD73 expression by B-CLL cells to the patients' clinical condition and their relationship with disease prognostic parameters and patients' outcome, aiming to apply them in routine clinical practice. The study included 40 newly diagnosed CLL patients and 20 controls. Quantification of CD73 and CD39 expression by CD19 positive cells was determined by flowcytometric analysis. A statistically significant lower percentage of lymphocytes expressing CD73 and higher ratio of CD39/CD73 in patients compared to controls were found. The percentage of cells expressing CD39 was higher in patients with lower tumor load, having a stable disease course and lymphocyte doubling time (LDT) >6 months. A cutoff point of <19% for CD73 expression, >2 for CD39/CD73ratio confirmed the diagnosis of CLL and a cutoff point > 41% for CD39 expression predicted clinically beneficial response to treatment. Thus, it is applicable to incorporate the detection of CD73 expression and the CD39/CD73 ratio into the CLL diagnostic panel and the use of CD39 as a prognostic marker for CLL. Key Words: Nucleotidases; B-CLL; CD73; CD39; ATP; Prognostic Factor; DiagnosticFactor 1. Catovsky D and Montserrat E. Chronic lymphocytic leukaemia and other B-cell disorders. In: Postgraduate haematology .By: Hoffbrand A, Catovsky D, Tuddenham E and Anthony R (eds), Blackwell Publishing, 6th edition 2011; 3:530-74. 2. Pulte D, Olson KE, Broekman MJ, Islam N, Ballard HS, Furman RR, Olson AE and Marcus AJ. CD39 activity correlates with stage and with platelets reactivity in chronic lymphocytic leukemia. J.Transl. Med, 2007; 4(5): 23-9. 3. Zhong X, Buddha M, Guidotti G, Kriz R, Somers W and Mosyak L. Expression, purification and crystallization of the ecto-enzymatic domain of rat E-NTPDase1 CD39. Acta Crystallogr Sect F Struct Biol Cryst Commun., 2008; 64(Pt 11):1063-5. 4. Heuts DP, Weissenborn MJ, Olkhov RV, Shaw AM, Gummadova J, Levy C and Scrutton NS. Crystal structure of a soluble form of human CD73 with ecto 5'nucleotidase activity. Chembiochem. 2012; 13(16):2384-91. 5. Serra S, Horenstein AL, Vaisitti T, Brusa D, Rossi D, Laurenti L, D'Arena G, Coscia M, Tripodo C, Inghirami G, Robson SC, Gaidano G, Malavasi F and Deaglio S.CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. Blood, 2011; 118(23): 6141-52. 6. Muller-Hermelink H, Montserrat E, Catovsky D, Campo E, Harris N and Stein H. Chronic lymphocytic leukemia/small lymphocytic lymphoma. In: WHO Classification of Tumors of Haematopoietic and lymphoid Tissues. By: Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, Thieele J and Vardiman J(eds). IARC, 4th edition 2008; 2:180-2. 7. Hallek M, Cheson B, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating M, Montserrat E, Rai K and Kipps T. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines. Blood 2008; 111(12): 5446-56. 8. Matutes E, Owusu-Ankomah K, Morilla R, Garcia Marco J, Houlihan A, Que TH and Catovsky D. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia,1994;8(10):1640-5. 9. Eichhorst B and Hallek M. Revision of the guidelines for diagnosis and therapy of chronic lymphocytic leukemia (CLL). Best Practice & Research Clinical Haematology; 2007; 20(3):469–77. 10. Huhn D, Von Schilling C, Wilhelm M, Ho A, Hallek M, Kuse R, Knauf W, Riedel U, Hinke A, Srock S, Serke S, Peschel C, Emmerich B for the German Chronic Lymphocytic Leukemia Study Group. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood, 2001; 98(5):1326-31. 11. Cappellari AR, Vasques GJ, Bavaresco L, Braganhol E and Battastini AM. Involvement of ecto-5'- nucleotidase/CD73 in U138MG glioma cell adhesion. Mol Cell Biochem., 2012; 359(1-2):315-22. 12. Rosi F, Carlucci F, Marinello E and Tabucchi E. Ecto-5’-nucleotidase in B-cell chronic lymphocytic leukemia. Biomed Pharmacother; 2002, 56:100-4. 13. Pulte D, Furman RR, Olson KE, Ballard HS and Marcus AJ. CD39 expression on T cells correlates with severity of diseases in patients with chronic lymphocytic leukemia. Lymphoma Myeloma leuk.,2011; 11(4):367-72.Abstract
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