Comparison of Surface CD52 and PD-L1 Expression in Pre- and Post-treatment Chronic Lymphocytic Leukemia (CLL) Patients
,
Abstract
Monoclonal antibodies targeting CD52 (alemtuzumab) and immune checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1, also known as CD274) have shown therapeutic potential in chronic lymphocytic leukemia (CLL). This study compared surface expression of CD52 and PD-L1 between treated and untreated patients with CLL.
A total of 67 patients were divided into 2 groups: a treatment group (n=23) comprising patients currently receiving therapy or in remission, and a follow-up group (n=44) consisting of untreated patients under regular monitoring. After obtaining ethical approval, peripheral blood samples were collected and analyzed by flow cytometry using monoclonal antibodies against CD5, CD19, CD23, CD52, and PD-L1.
No statistically significant differences were observed in CD19+, CD23+, or PD-L1 expression between the 2 groups. However, CD52+ expression was significantly higher in the treatment group (43.77% vs 25.46%). The treatment group also showed significantly higher CD5+ expression (35.05% vs 18.93%), while the CD23+CD52+ population was significantly higher in the follow-up group (43.30% vs 20.72%).
Higher levels of CD5+ and CD52+ may be associated with treatment requirement in patients with CLL. These findings are hypothesis-generating and require prospective validation in cohorts with survival endpoints. We do not claim prognostic equivalence to established markers such as TP53 disruption.
1. Eichhorst B, Robak T, Montserrat E, Ghia P, Niemann C,Kater A, et al. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2021;32(1):23-33.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30.
3. Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer. 2011;105(11):1684-92.
4. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-60.
5. Wierda WG, Brown J, Abramson JS, Awan F, Bilgrami SF, Bociek G, et al. Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 2.2024, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2024;22(3):175-204.
6. Kajüter H, Wellmann I, Khil L, Jöckel KH, Zhang C, Fink AM, et al. Survival of patients with chronic lymphocytic leukemia before and after the introduction of chemoimmunotherapy in Germany. Blood Cancer J. 2021;11(10):174.
7. Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, et al. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015;385(9980):1873-83.
8. Kristinsson SY, Dickman PW, Wilson WH, Caporaso N, Björkholm M, Landgren O. Improved survival in chronic lymphocytic leukemia in the past decade: a population-based study including 11,179 patients diagnosed between 1973-2003 in Sweden. Haematologica. 2009;94(9):1259-65.
9. Chang JE, Kahl BS. Bendamustine for treatment of chronic lymphocytic leukemia. Expert Opin Pharmacother. 2012;13(10):1495-505.
10. Robak T. Therapy of chronic lymphocytic leukaemia with purine nucleoside analogues: facts and controversies. Drugs Aging. 2005;22(12):983-1012.
11. Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-36.
12. Shanafelt TD, Wang XV, Kay NE, Hanson CA, O'Brien S, Barrientos J, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381(5):432-43.
13. Shadman M, Manzoor BS, Sail K, Tuncer HH, Allan JN, Ujjani C, et al. Treatment discontinuation patterns for patients with chronic lymphocytic leukemia in real-world settings: results from a multi-center international study. Clin Lymphoma Myeloma Leuk. 2023;23(7):515-26.
14. Preud'homme JL, Seligmann M. Anti-human immunoglobulin G activity of membrane-bound monoclonal immunoglobulin M in lymphoproliferative disorders. Proc Natl Acad Sci U S A. 1972;69(8):2132-5.
15. Stathopoulos G, Elliott EV. Formation of mouse or sheep red-blood-cell rosettes by lymphocytes from normal and leukaemic individuals. Lancet. 1974;1(7858):600-1.
16. Aisenberg AC, Bloch KJ, Long JC, Colvin RB. Reaction of normal human lymphocytes and chronic lymphocytic leukemia cells with an antithymocyte antiserum. Blood. 1973;41(3):417-23.
17. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group. J Clin Pathol. 1989;42(6):567-84.
18. Vosoughi T, Bagheri M, Hosseinzadeh M, Ehsanpour A, Davari N, Saki N. CD markers variations in chronic lymphocytic leukemia: new insights into prognosis. J Cell Physiol. 2019;234(11):19420-39.
19. Claus R, Lucas DM, Ruppert AS, Williams KE, Weng D, Patterson K, et al. Validation of ZAP-70 methylation and its relative significance in predicting outcome in chronic lymphocytic leukemia. Blood. 2014;124(1):42-8.
20. Claus R, Lucas DM, Stilgenbauer S, Ruppert AS, Yu L, Zucknick M, et al. Quantitative DNA methylation analysis identifies a single CpG dinucleotide important for ZAP-70 expression and predictive of prognosis in chronic lymphocytic leukemia. J Clin Oncol. 2012;30(20):2483-91.
21. Langerbeins P, Giza A, Robrecht S, Cramer P, von Tresckow J, Al-Sawaf O, et al. Reassessing the chronic lymphocytic leukemia international prognostic index in the era of targeted therapies. Blood. 2024;143(25):2588-98.
22. Soumerai JD, Ni A, Xing G, Huang J, Furman RR, Jones J, et al. Evaluation of the CLL-IPI in relapsed and refractory chronic lymphocytic leukemia in idelalisib phase-3 trials. Leuk Lymphoma. 2019;60(6):1438-46.
23. Molica S, Giannarelli D, Mirabelli R, Levato L, Shanafelt TD. Chronic lymphocytic leukemia international prognostic index (CLL-IPI) in patients receiving chemoimmuno or targeted therapy: a systematic review and meta-analysis. Ann Hematol. 2018;97(10):2005-8.
24. Molica S. Chronic lymphocytic leukemia prognostic models in real life: still a long way off. Expert Rev Hematol. 2021;14(2):137-41.
25. Klabusay M, Sukova V, Coupek P, Brychtova Y, Mayer J. Different levels of CD52 antigen expression evaluated by quantitative fluorescence cytometry are detected on B-lymphocytes, CD 34+ cells and tumor cells of patients with chronic B-cell lymphoproliferative diseases. Cytometry B Clin Cytom. 2007;72(5):363-70.
26. Xia MQ, Hale G, Lifely MR, Ferguson MA, Campbell D, Packman L, Waldmann H. Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem J. 1993;293 ( Pt 3)(Pt 3):633-40.
27. Waldmann H. A personal history of the CAMPATH-1H antibody. Med Oncol. 2002;19 Suppl:S3-9.
28. Carlo-Stella C, Guidetti A, Di Nicola M, Longoni P, Cleris L, Lavazza C, et al. CD52 antigen expressed by malignant plasma cells can be targeted by alemtuzumab in vivo in NOD/SCID mice. Exp Hematol. 2006;34(6):721-7.
29. Albitar M, Do K-A, Johnson MM, Giles FJ, Jilani I, O'Brien S, et al. Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies. Cancer. 2004;101(5):999-1008.
30. Vojdeman FJ, Herman SEM, Kirkby N, Wiestner A, van t’ Veer MB, Tjønnfjord GE, et al. Soluble CD52 is an indicator of disease activity in chronic lymphocytic leukemia. Leukemia & Lymphoma. 2017;58(10):2356-62.
31. Pevna M, Doubek M, Coupek P, Stehlikova O, Klabusay M. Residual cancer lymphocytes in patients with chronic lymphocytic leukemia after therapy show increased expression of surface antigen CD52 detected using quantitative fluorescence cytometry. Clinical Lymphoma Myeloma and Leukemia. 2014;14(5):411-8.
32. Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020;10(3):727-42.
33. Lenouvel D, González-Moles M, Talbaoui A, Ramos-García P, González-Ruiz L, Ruiz-Ávila I, Gil-Montoya JA. An update of knowledge on PD-L1 in head and neck cancers: physiologic, prognostic and therapeutic perspectives. Oral Dis. 2020;26(3):511-26.
34. Gou Q, Dong C, Xu H, Khan B, Jin J, Liu Q, et al. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis. 2020;11(11):955.
35. Fujiwara M, Garo LP, Murugaiyan G. PD1 blockade in cancer: impact on myeloid cells. Trends Cancer. 2020;6(6):443-4.
36. Qorri B, Geraci J, Tsay M, Cumbaa C, Alphs L, Pani L. Revealing heterogeneity in chronic lymphocytic leukemia: AI-driven insights into aggressive and indolent disease subtypes. Journal of Clinical Oncology. 2024;42(16_suppl):e19029-e.
37. Surveillance Epidemiology ER. Cancer stat facts: leukemia—chronic lymphocytic leukemia (CLL). 2021.
38. Mukkamalla SKR, Taneja A, Malipeddi D, Master SR. Chronic lymphocytic leukemia. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC.; 2024.
39. Urso A, Martino EA, Cuneo A, Gentile M, Rigolin GM. Chronic lymphocytic leukemia: prognostic factors in the era of novel drugs. Cancers. 2024;16(15):2732.
40. Pevna M, Doubek M, Coupek P, Stehlikova O, Klabusay M. Residual cancer lymphocytes in patients with chronic lymphocytic leukemia after therapy show increased expression of surface antigen CD52 detected using quantitative fluorescence cytometry. Clin Lymphoma Myeloma Leuk. 2014;14(5):411-8.
41. Paulick MG, Bertozzi CR. The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins. Biochemistry. 2008;47(27):6991-7000.
42. Chang BY, Francesco M, De Rooij MF, Magadala P, Steggerda SM, Huang MM, et al. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013;122(14):2412-24.
43. Bandala-Sanchez E, Zhang Y, Reinwald S, Dromey JA, Lee BH, Qian J, et al. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nat Immunol. 2013;14(7):741-8.
44. Albitar M, Do KA, Johnson MM, Giles FJ, Jilani I, O'Brien S, et al. Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies. Cancer. 2004;101(5):999-1008.
45. Alatrash G, Albitar M, O'Brien S, Wang X, Manshouri T, Faderl S, et al. Circulating CD52 and CD20 levels at end of treatment predict for progression and survival in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab (FCR). Br J Haematol. 2010;148(3):386-93.
46. Vojdeman FJ, Herman SEM, Kirkby N, Wiestner A, van T' Veer MB, Tjønnfjord GE, et al. Soluble CD52 is an indicator of disease activity in chronic lymphocytic leukemia. Leuk Lymphoma. 2017;58(10):2356-62.
47. Salmaninejad A, Valilou SF, Shabgah AG, Aslani S, Alimardani M, Pasdar A, Sahebkar A. PD-1/PD-L1 pathway: basic biology and role in cancer immunotherapy. J Cell Physiol. 2019;234(10):16824-37.
48. Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol. 2006;27(4):195-201.
49. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517-9.
50. Li JH, Pang NN, Zhang ZH, Zhang R, Chen G, Qu JH. [PD-1/PD-L1 expression and its implications in patients with chronic lymphocytic leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2017;38(3):198-203.
51. Gamaleldin MA, Ghallab OM, Nadwan EA, Abo Elwafa RA. PD-1 and PD-L1 gene expressions and their association with Epstein-Barr virus infection in chronic lymphocytic leukemia. Clin Transl Oncol. 2021;23(11):2309-22.
52. Wang Y, Sinha S, Wellik LE, Secreto CR, Rech KL, Call TG, et al. Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome. Blood Cancer J. 2021;11(5):86.
53. Augé H, Notarantonio AB, Morizot R, Quinquenel A, Fornecker LM, Hergalant S, et al. Microenvironment remodeling and subsequent clinical implications in diffuse large B-cell histologic variant of Richter syndrome. Front Immunol. 2020;11:594841.
54. Masoud R, Eladl AE, El-Ashwah S, Abbas A, Kandil W. Clinicopathological study of PD-1/PD-L1 expression in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with emphasis on large B-cell Richter transformation. Asian Pac J Cancer Prev. 2023;24(12):4243-52.
55. Kondo K, Shaim H, Thompson PA, Burger JA, Keating M, Estrov Z, et al. Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B-cell function and inhibition of the PD-1/PD-L1 pathway. Leukemia. 2018;32(4):960-70.
56. Cubillos-Zapata C, Avendaño-Ortiz J, Córdoba R, Hernández-Jiménez E, Toledano V, Pérez de Diego R, López-Collazo E. Ibrutinib as an antitumor immunomodulator in patients with refractory chronic lymphocytic leukemia. Oncoimmunology. 2016;5(12):e1242544.
57. Kondo K, Burger JA, Micheal K, Tran J, Muftuoglu M, Daher M, et al. Ibrutinib can modulate the T cell response in chronic lymphocytic leukemia by reducing PD1/PDL1 interactions. Blood. 2015;126(23):1737.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30.
3. Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer. 2011;105(11):1684-92.
4. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-60.
5. Wierda WG, Brown J, Abramson JS, Awan F, Bilgrami SF, Bociek G, et al. Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 2.2024, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2024;22(3):175-204.
6. Kajüter H, Wellmann I, Khil L, Jöckel KH, Zhang C, Fink AM, et al. Survival of patients with chronic lymphocytic leukemia before and after the introduction of chemoimmunotherapy in Germany. Blood Cancer J. 2021;11(10):174.
7. Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, et al. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015;385(9980):1873-83.
8. Kristinsson SY, Dickman PW, Wilson WH, Caporaso N, Björkholm M, Landgren O. Improved survival in chronic lymphocytic leukemia in the past decade: a population-based study including 11,179 patients diagnosed between 1973-2003 in Sweden. Haematologica. 2009;94(9):1259-65.
9. Chang JE, Kahl BS. Bendamustine for treatment of chronic lymphocytic leukemia. Expert Opin Pharmacother. 2012;13(10):1495-505.
10. Robak T. Therapy of chronic lymphocytic leukaemia with purine nucleoside analogues: facts and controversies. Drugs Aging. 2005;22(12):983-1012.
11. Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-36.
12. Shanafelt TD, Wang XV, Kay NE, Hanson CA, O'Brien S, Barrientos J, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381(5):432-43.
13. Shadman M, Manzoor BS, Sail K, Tuncer HH, Allan JN, Ujjani C, et al. Treatment discontinuation patterns for patients with chronic lymphocytic leukemia in real-world settings: results from a multi-center international study. Clin Lymphoma Myeloma Leuk. 2023;23(7):515-26.
14. Preud'homme JL, Seligmann M. Anti-human immunoglobulin G activity of membrane-bound monoclonal immunoglobulin M in lymphoproliferative disorders. Proc Natl Acad Sci U S A. 1972;69(8):2132-5.
15. Stathopoulos G, Elliott EV. Formation of mouse or sheep red-blood-cell rosettes by lymphocytes from normal and leukaemic individuals. Lancet. 1974;1(7858):600-1.
16. Aisenberg AC, Bloch KJ, Long JC, Colvin RB. Reaction of normal human lymphocytes and chronic lymphocytic leukemia cells with an antithymocyte antiserum. Blood. 1973;41(3):417-23.
17. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group. J Clin Pathol. 1989;42(6):567-84.
18. Vosoughi T, Bagheri M, Hosseinzadeh M, Ehsanpour A, Davari N, Saki N. CD markers variations in chronic lymphocytic leukemia: new insights into prognosis. J Cell Physiol. 2019;234(11):19420-39.
19. Claus R, Lucas DM, Ruppert AS, Williams KE, Weng D, Patterson K, et al. Validation of ZAP-70 methylation and its relative significance in predicting outcome in chronic lymphocytic leukemia. Blood. 2014;124(1):42-8.
20. Claus R, Lucas DM, Stilgenbauer S, Ruppert AS, Yu L, Zucknick M, et al. Quantitative DNA methylation analysis identifies a single CpG dinucleotide important for ZAP-70 expression and predictive of prognosis in chronic lymphocytic leukemia. J Clin Oncol. 2012;30(20):2483-91.
21. Langerbeins P, Giza A, Robrecht S, Cramer P, von Tresckow J, Al-Sawaf O, et al. Reassessing the chronic lymphocytic leukemia international prognostic index in the era of targeted therapies. Blood. 2024;143(25):2588-98.
22. Soumerai JD, Ni A, Xing G, Huang J, Furman RR, Jones J, et al. Evaluation of the CLL-IPI in relapsed and refractory chronic lymphocytic leukemia in idelalisib phase-3 trials. Leuk Lymphoma. 2019;60(6):1438-46.
23. Molica S, Giannarelli D, Mirabelli R, Levato L, Shanafelt TD. Chronic lymphocytic leukemia international prognostic index (CLL-IPI) in patients receiving chemoimmuno or targeted therapy: a systematic review and meta-analysis. Ann Hematol. 2018;97(10):2005-8.
24. Molica S. Chronic lymphocytic leukemia prognostic models in real life: still a long way off. Expert Rev Hematol. 2021;14(2):137-41.
25. Klabusay M, Sukova V, Coupek P, Brychtova Y, Mayer J. Different levels of CD52 antigen expression evaluated by quantitative fluorescence cytometry are detected on B-lymphocytes, CD 34+ cells and tumor cells of patients with chronic B-cell lymphoproliferative diseases. Cytometry B Clin Cytom. 2007;72(5):363-70.
26. Xia MQ, Hale G, Lifely MR, Ferguson MA, Campbell D, Packman L, Waldmann H. Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem J. 1993;293 ( Pt 3)(Pt 3):633-40.
27. Waldmann H. A personal history of the CAMPATH-1H antibody. Med Oncol. 2002;19 Suppl:S3-9.
28. Carlo-Stella C, Guidetti A, Di Nicola M, Longoni P, Cleris L, Lavazza C, et al. CD52 antigen expressed by malignant plasma cells can be targeted by alemtuzumab in vivo in NOD/SCID mice. Exp Hematol. 2006;34(6):721-7.
29. Albitar M, Do K-A, Johnson MM, Giles FJ, Jilani I, O'Brien S, et al. Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies. Cancer. 2004;101(5):999-1008.
30. Vojdeman FJ, Herman SEM, Kirkby N, Wiestner A, van t’ Veer MB, Tjønnfjord GE, et al. Soluble CD52 is an indicator of disease activity in chronic lymphocytic leukemia. Leukemia & Lymphoma. 2017;58(10):2356-62.
31. Pevna M, Doubek M, Coupek P, Stehlikova O, Klabusay M. Residual cancer lymphocytes in patients with chronic lymphocytic leukemia after therapy show increased expression of surface antigen CD52 detected using quantitative fluorescence cytometry. Clinical Lymphoma Myeloma and Leukemia. 2014;14(5):411-8.
32. Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020;10(3):727-42.
33. Lenouvel D, González-Moles M, Talbaoui A, Ramos-García P, González-Ruiz L, Ruiz-Ávila I, Gil-Montoya JA. An update of knowledge on PD-L1 in head and neck cancers: physiologic, prognostic and therapeutic perspectives. Oral Dis. 2020;26(3):511-26.
34. Gou Q, Dong C, Xu H, Khan B, Jin J, Liu Q, et al. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis. 2020;11(11):955.
35. Fujiwara M, Garo LP, Murugaiyan G. PD1 blockade in cancer: impact on myeloid cells. Trends Cancer. 2020;6(6):443-4.
36. Qorri B, Geraci J, Tsay M, Cumbaa C, Alphs L, Pani L. Revealing heterogeneity in chronic lymphocytic leukemia: AI-driven insights into aggressive and indolent disease subtypes. Journal of Clinical Oncology. 2024;42(16_suppl):e19029-e.
37. Surveillance Epidemiology ER. Cancer stat facts: leukemia—chronic lymphocytic leukemia (CLL). 2021.
38. Mukkamalla SKR, Taneja A, Malipeddi D, Master SR. Chronic lymphocytic leukemia. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC.; 2024.
39. Urso A, Martino EA, Cuneo A, Gentile M, Rigolin GM. Chronic lymphocytic leukemia: prognostic factors in the era of novel drugs. Cancers. 2024;16(15):2732.
40. Pevna M, Doubek M, Coupek P, Stehlikova O, Klabusay M. Residual cancer lymphocytes in patients with chronic lymphocytic leukemia after therapy show increased expression of surface antigen CD52 detected using quantitative fluorescence cytometry. Clin Lymphoma Myeloma Leuk. 2014;14(5):411-8.
41. Paulick MG, Bertozzi CR. The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins. Biochemistry. 2008;47(27):6991-7000.
42. Chang BY, Francesco M, De Rooij MF, Magadala P, Steggerda SM, Huang MM, et al. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013;122(14):2412-24.
43. Bandala-Sanchez E, Zhang Y, Reinwald S, Dromey JA, Lee BH, Qian J, et al. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nat Immunol. 2013;14(7):741-8.
44. Albitar M, Do KA, Johnson MM, Giles FJ, Jilani I, O'Brien S, et al. Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies. Cancer. 2004;101(5):999-1008.
45. Alatrash G, Albitar M, O'Brien S, Wang X, Manshouri T, Faderl S, et al. Circulating CD52 and CD20 levels at end of treatment predict for progression and survival in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab (FCR). Br J Haematol. 2010;148(3):386-93.
46. Vojdeman FJ, Herman SEM, Kirkby N, Wiestner A, van T' Veer MB, Tjønnfjord GE, et al. Soluble CD52 is an indicator of disease activity in chronic lymphocytic leukemia. Leuk Lymphoma. 2017;58(10):2356-62.
47. Salmaninejad A, Valilou SF, Shabgah AG, Aslani S, Alimardani M, Pasdar A, Sahebkar A. PD-1/PD-L1 pathway: basic biology and role in cancer immunotherapy. J Cell Physiol. 2019;234(10):16824-37.
48. Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol. 2006;27(4):195-201.
49. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517-9.
50. Li JH, Pang NN, Zhang ZH, Zhang R, Chen G, Qu JH. [PD-1/PD-L1 expression and its implications in patients with chronic lymphocytic leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2017;38(3):198-203.
51. Gamaleldin MA, Ghallab OM, Nadwan EA, Abo Elwafa RA. PD-1 and PD-L1 gene expressions and their association with Epstein-Barr virus infection in chronic lymphocytic leukemia. Clin Transl Oncol. 2021;23(11):2309-22.
52. Wang Y, Sinha S, Wellik LE, Secreto CR, Rech KL, Call TG, et al. Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome. Blood Cancer J. 2021;11(5):86.
53. Augé H, Notarantonio AB, Morizot R, Quinquenel A, Fornecker LM, Hergalant S, et al. Microenvironment remodeling and subsequent clinical implications in diffuse large B-cell histologic variant of Richter syndrome. Front Immunol. 2020;11:594841.
54. Masoud R, Eladl AE, El-Ashwah S, Abbas A, Kandil W. Clinicopathological study of PD-1/PD-L1 expression in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with emphasis on large B-cell Richter transformation. Asian Pac J Cancer Prev. 2023;24(12):4243-52.
55. Kondo K, Shaim H, Thompson PA, Burger JA, Keating M, Estrov Z, et al. Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B-cell function and inhibition of the PD-1/PD-L1 pathway. Leukemia. 2018;32(4):960-70.
56. Cubillos-Zapata C, Avendaño-Ortiz J, Córdoba R, Hernández-Jiménez E, Toledano V, Pérez de Diego R, López-Collazo E. Ibrutinib as an antitumor immunomodulator in patients with refractory chronic lymphocytic leukemia. Oncoimmunology. 2016;5(12):e1242544.
57. Kondo K, Burger JA, Micheal K, Tran J, Muftuoglu M, Daher M, et al. Ibrutinib can modulate the T cell response in chronic lymphocytic leukemia by reducing PD1/PDL1 interactions. Blood. 2015;126(23):1737.
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How to Cite
1.
Khorramian H, Nikbakht Brujeni G, Mortazavi P, Razavi SM. Comparison of Surface CD52 and PD-L1 Expression in Pre- and Post-treatment Chronic Lymphocytic Leukemia (CLL) Patients. Iran J Allergy Asthma Immunol. 2026;:1-12.
