BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner

• Published in: Frontiers in oncology 2019-07, Vol.9, p.594-594
• Main Authors: Sevdali, Eirini, Katsantoni, Eleni, Smulski, Cristian R, Moschovi, Maria, Palassopoulou, Maria, Kolokotsa, Eleni-Nefeli, Argentou, Nikoletta, Giannakoulas, Nikolaos, Adamaki, Maria, Vassilopoulos, Georgios, Polychronopoulou, Sophia, Germenis, Anastasios E, Eibel, Hermann, Speletas, Matthaios
• Format: Article
• Language: English
• Subjects: apoptosis; B-ALL; BAFFR; E2A-PBX1; glucocorticoids; Oncology
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2019.00594

BAFF, APRIL and their receptors regulate the survival, maturation and homeostasis of mature B-cells. Despite the lack of a functional role of BAFF/APRIL system during normal early B-cell development, previous studies indicated a contribution of these molecules in the pathogenesis of B-lineage acute lymphoblastic leukemia (B-ALL). Here, we evaluated the expression of this system in B-ALL and its involvement in spontaneous and drug-induced apoptosis of B-lymphoblasts, taking into consideration the distinct disease subtypes. We found that BAFFR is the most predominant aberrantly expressed receptor in B-ALL and that its expression, along with BCMA and APRIL, positively correlates with the maturation stage of B-lymphoblasts. Moreover, the binding of the E2A-PBX1 chimeric protein to the promoter suggests that the transcriptional activator promotes the increase in expression observed in about 50% of pre-B-ALL patients carrying the translocation. BAFF binding to BAFFR led to the processing of NF-κB2 p100 in pre-B ALL cells suggesting that BAFFR can activate the NF-κB2 pathway in pre-B ALL cells. Surprisingly, we found that BAFF treatment promotes the cell death of primary BCR-ABL BAFFR pre-B-lymphoblasts in adult B-ALL. It also enhances glucocorticoid-induced apoptosis in the E2A-PBX1 pre-B-ALL cell line 697. These data suggest that BAFF/BAFFR signaling in B-ALL cells differs from normal B cells and that it may affect the pathogenesis of the disease.