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

Abstract

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 BAFFR promoter suggests that the transcriptional activator promotes the increase in BAFFR expression observed in about 50% of pre-B-ALL patients carrying the t (1, 19) 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.

• Authors: Eirini Sevdali, Eleni Katsantoni, Cristian R Smulski, Maria Moschovi, Maria Palassopoulou, Eleni-Nefeli Kolokotsa, Nikoletta Argentou, Nikolaos Giannakoulas, Maria Adamaki, Georgios Vassilopoulos, Sophia Polychronopoulou, Anastasios E Germenis, Hermann Eibel, Matthaios Speletas
• Journal: Frontiers in oncology (Front Oncol) Vol. 9 Pg. 594 ( 2019) ISSN: 2234-943X [Print] Switzerland
• PMID: 31380267 (Publication Type: Journal Article)