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Indian Journal of Hematology and Blood Transfusion

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01-04-2019 | Original Article

Prognostic Significance of Serum BAFF, APRIL, TACI and BCMA Levels in Chronic Lymphocytic Leukemia

Authors: İlay Berke Menteşe, Zeynep Arzu Yegin, Sanem Gökçen, Zübeyde Nur Özkurt, Münci Yağcı

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 2/2019

Abstract

As chronic lymphocytic leukemia (CLL) has a variable disease course, novel prognostic markers and risk assessment models are being developed in order to identify high-risk patients who may need early treatment. The two tumor necrosis factor family proteins BAFF and APRIL and their receptors BAFF-R, TACI and BCMA are considered to play a critical role in the survival of normal B cells. In order to highlight the pathophysiological role of this complicated biological network, we aimed to analyze the potential prognostic effects of BAFF, APRIL, TACI and BCMA in CLL patients. We investigated the prognostic impact of serum BCMA, TACI, BAFF and APRIL levels in 129 newly diagnosed CLL patients [median age: 64 (39–88) years; male/female: 85/44]. Serum BAFF, TACI and BCMA levels were significantly lower in the patient group compared to the control group (p < 0.001), while serum APRIL level did not differ significantly between two groups (p > 0.05). Serum BCMA [(p = 0.029; r = 0.208)] and TACI levels [(p = 0.011; r = 0.241)] were positively correlated with serum free light chain ratio. Serum BAFF [(p = 0.008; r = − 0.236)] and BCMA [(p = 0.042; r = − 0.183)] levels were negatively correlated with Rai stage. Overall survival (OS) was relatively better in patients with low serum BAFF levels [60 (1–187) months vs 39.5 (0–256) months; p = 0.063]. Probability of OS was higher in patients with low BAFF levels when compared to patients with normal levels, without statistical significance (53.6% vs 23.6%; p > 0.05). Large prospective studies are needed to validate the prognostic role of this essential biological pathway in CLL.

Andersen BL, Goyal NG, Weiss DM, Westbrook TD, Maddocks KJ, Byrd JC, Johnson AJ (2018) Cells, cytokines, chemokines, and cancer stress: a biobehavioral study of patients with chronic lymphocytic leukemia. Cancer 124(15):3240–3248CrossRefPubMedPubMedCentral

Hallek M (2015) Chronic lymphocytic leukemia: 2015 update on diagnosis, risk stratification, and treatment. Am J Hematol 90(5):446–460CrossRefPubMed

Jasek M, Bojarska-Junak A, Wagner M, Sobczyński M, Wołowiec D, Roliński J, Karabon L, Kuśnierczyk P (2016) Association of variants in BAFF (rs9514828 and rs1041569) and BAFF-R (rs61756766) genes with the risk of chronic lymphocytic leukemia. Tumour Biol 37(10):13617–13626CrossRefPubMedPubMedCentral

Cramer P, Hallek M (2011) Prognostic factors in chronic lymphocytic leukemia-what do we need to know? Nat Rev Clin Oncol 8(1):38–47CrossRefPubMed

Burger JA, Gribben JG (2014) The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell malignancies: insight into disease biology and new targeted therapies. Semin Cancer Biol 24:71–81CrossRefPubMed

Nicoletti AM, Kenny CH, Khalil AM, Pan Q, Ralph KL, Ritchie J, Venkataramani S, Presky DH, DeWire SM, Brodeur SR (2016) Unexpected potency differences between B-cell-activating factor (BAFF) antagonist antibodies against various forms of BAFF: trimer, 60-Mer, and membrane-bound. J Pharmacol Exp Ther 359(1):37–44CrossRefPubMed

Li YJ, Li ZM, Xia ZJ, Li S, Xia Y, Huang HQ, Huang JJ, Yi PY, Jiang WQ (2015) High APRIL but not BAFF serum levels are associated with poor outcome in patients with follicular lymphoma. Ann Hematol 94(1):79–88CrossRefPubMed

Moreaux J, Legouffe E, Jourdan E, Quittet P, Rème T, Lugagne C, Moine P, Rossi JF, Klein B, Tarte K (2004) BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood 103(8):3148–3157CrossRefPubMed

Chiu A, Xu W, He B, Dillon SR, Gross JA, Sievers E, Qiao X, Santini P, Hyjek E, Lee JW, Cesarman E, Chadburn A, Knowles DM, Cerutti A (2007) Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL. Blood 109(2):729–739CrossRefPubMedPubMedCentral

10.

Oden F, Marino SF, Brand J, Scheu S, Kriegel C, Olal D, Takvorian A, Westermann J, Yilmaz B, Hinz M, Daumke O, Höpken UE, Müller G, Lipp M (2015) Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma. Mol Oncol 9(7):1348–1358CrossRefPubMedPubMedCentral

11.

Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, Oregon-Romero E, Machado-Contreras JR, Muñoz-Valle JF, Orozco-López M, Marín-Rosales M, Palafox-Sánchez CA (2015) Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus 25(6):582–592CrossRefPubMed

12.

Nagatani K, Itoh K, Nakajima K, Kuroki H, Katsuragawa Y, Mochizuki M, Aotsuka S, Mimori A (2007) Rheumatoid arthritis fibroblast-like synoviocytes express BCMA and are stimulated by APRIL. Arthritis Rheum 56(11):3554–3563CrossRefPubMed

13.

Tsuji S, Cortesão C, Bram RJ, Platt JL, Cascalho M (2011) TACI deficiency impairs sustained Blimp-1 expression in B cells decreasing long-lived plasma cells in the bone marrow. Blood 118(22):5832–5839CrossRefPubMedPubMedCentral

14.

Dou H, Yan Z, Zhang M, Xu X (2016) APRIL, BCMA and TACI proteins are abnormally expressed in non-small cell lung cancer. Oncol Lett 12(5):3351–3355CrossRefPubMedPubMedCentral

15.

He B, Chadburn A, Jou E, Schattner EJ, Knowles DM, Cerutti A (2004) Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL. J Immunol 172(5):3268–3279CrossRefPubMed

16.

Kern C, Cornuel JF, Billard C, Tang R, Rouillard D, Stenou V, Defrance T, Ajchenbaum-Cymbalista F, Simonin PY, Feldblum S, Kolb JP (2004) Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway. Blood 103(2):679–688CrossRefPubMed

17.

Nishio M, Endo T, Tsukada N, Ohata J, Kitada S, Reed JC, Zvaifler NJ, Kipps TJ (2005) Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1alpha. Blood 106(3):1012–1020CrossRefPubMedPubMedCentral

18.

Endo T, Nishio M, Enzler T, Cottam HB, Fukuda T, James DF, Karin M, Kipps TJ (2007) BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through activation of the canonical NF-kappaB pathway. Blood 109(2):703–710CrossRefPubMed

19.

Cols M, Barra CM, He B, Puga I, Xu W, Chiu A, Tam W, Knowles DM, Dillon SR, Leonard JP, Furman RR, Chen K, Cerutti A (2012) Stromal endothelial cells establish a bidirectional crosstalk with chronic lymphocytic leukemia cells through the TNF-related factors BAFF, APRIL, and CD40L. J Immunol 188(12):6071–6083CrossRefPubMedPubMedCentral

20.

Lascano V, Guadagnoli M, Schot JG, Luijks DM, Guikema JE, Cameron K, Hahne M, Pals S, Slinger E, Kipps TJ, van Oers MH, Eldering E, Medema JP, Kater AP (2013) Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI interaction in the TCL1 transgenic mouse model. Blood 122(24):3960–3963CrossRefPubMedPubMedCentral

21.

Mhawech-Fauceglia P, Allal A, Odunsi K, Andrews C, Herrmann FR, Huard B (2008) Role of the tumour necrosis family ligand APRIL in solid tumour development: retrospective studies in bladder, ovarian and head and neck carcinomas. Eur J Cancer 44(15):2097–2100CrossRefPubMed

22.

Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer JL, Schneider P, Bornand T, Holler N, French LE, Sordat B, Rimoldi D, Tschopp J (1998) APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J Exp Med 188(6):1185–1190CrossRefPubMedPubMedCentral

23.

Lee C, Park JW, Suh JH, Moon KC (2015) High expression of APRIL correlates with poor prognosis in clear cell renal cell carcinoma. Pathol Res Pract 211(11):824–828CrossRefPubMed

24.

Qian Z, Qingshan C, Chun J, Huijun Z, Feng L, Qiang W, Qiang X, Min Z (2014) High expression of TNFSF13 in tumor cells and fibroblasts is associated with poor prognosis in non–small cell lung cancer. Am J Clin Pathol 141(2):226–233CrossRefPubMed

25.

Wang G, Wang F, Ding W, Wang J, Jing R, Li H, Wang X, Wang Y, Ju S, Wang H (2013) APRIL induces tumorigenesis and metastasis of colorectal cancer cells via activation of the PI3K/Akt pathway. PLoS ONE 8(1):e55298CrossRefPubMedPubMedCentral

26.

García-Castro A, Zonca M, Florindo-Pinheiro D, Carvalho-Pinto CE, Cordero A, Gutiérrez del Fernando B, García-Grande A, Mañes S, Hahne M, González-Suárez E, Planelles L (2015) APRIL promotes breast tumor growth and metastasis and is associated with aggressive basal breast cancer. Carcinogenesis 36(5):574–584CrossRefPubMed

27.

Wang F, Chen L, Ding W, Wang G, Wu Y, Wang J, Luo L, Cong H, Wang Y, Ju S, Shao J, Wang H (2011) Serum APRIL a potential tumor marker in pancreatic cancer. Clin Chem Lab Med 49(10):1715–1719CrossRefPubMed

28.

Mamara A, Germenis AE, Kompoti M, Palassopoulou M, Mandala E, Banti A, Giannakoulas N, Speletas M (2015) TACI expression and signaling in chronic lymphocytic leukemia. J Immunol Res 478753

29.

Kyrtsonis MC, Sarris K, Koulieris E, Maltezas D, Nikolaou E, Angelopoulou MK, Bartzis V, Tzenou T, Dimou M, Siakandaris MP, Viniou NA, Sachanas S, Kalpadakis C, Sfikakis PP, Pangalis GA, Panayiotidis P (2014) Serum soluble TACI, a BLyS receptor is a powerful prognostic marker of outcome in chronic lymphocytic leukemia. Biomed Res Int 159632

30.

Planelles L, Castillo-Gutiérrez S, Medema JP, Morales-Luque A, Merle-Béral H, Hahne M (2017) APRIL but not BLyS serum levels are increased in chronic lymphocytic leukemia: prognostic relevance of APRIL for survival. Haematologica 92(9):1284–1285CrossRef

31.

Haiat S, Billard C, Quiney C, Ajchenbaum-Cymbalista F, Kolb JP (2006) Role of BAFF and APRIL in human B-cell chronic lymphocytic leukaemia. Immunology 118(3):281–292CrossRefPubMedPubMedCentral

32.

Molica S, Digiesi G, Battaglia C, Cutrona G, Antenucci A, Molica M, Giannarelli D, Sperduti I, Gentile M, Morabito F, Ferrarini M (2010) BAFF serum level predicts time to first treatment in early chronic lymphocytic leukemia. Eur J Haematol 85(4):314–320CrossRefPubMed

33.

Saulep-Easton D, Vincent FB, Quah PS, Wei A, Ting SB, Croce CM, Tam C, Mackay F (2016) The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells. Leukemia 30(1):163–172CrossRefPubMed

34.

Bojarska-Junak A, Hus I, Chocholska S, Wasik-Szczepanek E, Sieklucka M, Dmoszyńska A, Roliński J (2009) BAFF and APRIL expression in B-cell chronic lymphocytic leukemia: correlation with biological and clinical features. Leuk Res 33(10):1319–1327CrossRefPubMed

35.

Ferrer G, Hodgson K, Pereira A, Juan M, Elena M, Colomer D, Roué G, Aymerich M, Baumann T, Montserrat E, Moreno C (2011) Combined analysis of levels of serum B-cell activating factor and a proliferation-inducing ligand as predictor of disease progression in patients with chronic lymphocytic leukemia. Leuk Lymphoma 52(11):2064–2068CrossRefPubMed

36.

Kreuzaler M, Rauch M, Salzer U, Birmelin J, Rizzi M, Grimbacher B, Plebani A, Lougaris V, Quinti I, Thon V, Litzman J, Schlesier M, Warnatz K, Thiel J, Rolink AG, Eibel H (2012) Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. J Immunol 188(1):497–503CrossRefPubMed

37.

Bojarska-Junak A, Hus I, Sieklucka M, Surdacka A, Kusz ML, Wasik-Szczepanek E, Dmoszynska A, Rolinski J (2011) The role of TACI expression in chronic lymphocytic leukemia. Cent Eur J Immunol 36(1):46–50

38.

Malavasi F, Deaglio S, Damle R, Cutrona G, Ferrarini M, Chiorazzi N (2011) CD38 and chronic lymphocytic leukemia: a decade later. Blood 118(13):3470–3478CrossRefPubMedPubMedCentral

39.

Burgler S (2015) Role of CD38 expression in diagnosis and pathogenesis of chronic lymphocytic leukemia and its potential as therapeutic target. Crit Rev Immunol 35(5):417–432CrossRefPubMed

40.

Ferrer G, Bosch R, Hodgson K, Tejero R, Roué G, Colomer D, Montserrat E, Moreno C (2014) B cell activation through CD40 and IL4R ligation modulates the response of chronic lymphocytic leukaemia cells to BAFF and APRIL. Br J Haematol 164(4):570–578CrossRefPubMed

Title: Prognostic Significance of Serum BAFF, APRIL, TACI and BCMA Levels in Chronic Lymphocytic Leukemia
Authors: İlay Berke Menteşe
Zeynep Arzu Yegin
Sanem Gökçen
Zübeyde Nur Özkurt
Münci Yağcı
Publication date: 01-04-2019
Publisher: Springer India
Published in: Indian Journal of Hematology and Blood Transfusion / Issue 2/2019
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI: https://doi.org/10.1007/s12288-018-1029-7

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