Prognostic Significance of Serum BAFF, APRIL, TACI and BCMA Levels in Chronic Lymphocytic Leukemia
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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.
KeywordsChronic lymphocytic leukemia BAFF APRIL BCMA TACI Prognosis
İBM: Hypothesis and design, data collection, manuscript writing; ZAY: Hypothesis and design, manuscript writing, statistical analysis, manuscript review; SG: Laboratory analysis, method design; ZNÖ: Data collection, manuscript review; MY: Data collection, manuscript review.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no competing interests.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Human and Animal Rights
This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
- 6.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):37–44CrossRefGoogle Scholar
- 9.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):729–739CrossRefGoogle Scholar
- 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):1348–1358CrossRefGoogle Scholar
- 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):582–592CrossRefGoogle Scholar
- 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):6071–6083CrossRefGoogle Scholar
- 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):3960–3963CrossRefGoogle Scholar
- 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):574–584CrossRefGoogle Scholar
- 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 478753Google Scholar
- 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 159632Google Scholar
- 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):2064–2068CrossRefGoogle Scholar
- 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):497–503CrossRefGoogle Scholar
- 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):46–50Google Scholar