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

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 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 BAFFR promoter, suggests a potential mechanism explaining the increased BAFFR expression observed in a proportion of pre-B-ALL patients. Activation of the NF-kappaB2 pathway in pre-B ALL cells in response to binding of BAFF to BAFFR confirms that the prematurely expressed BAFFR has the potential to activate downstream pathways. Surprisingly, we found that BAFF treatment promotes the cell death of primary BCR-ABL+ BAFFR+ pre-B-lymphoblasts in adult B-ALL as well as the glucocorticoid-induced apoptosis in the E2A-PBX1+ pre-B-ALL cell line 697. These data suggest a distinct role of BAFF/APRIL system in B-ALL pathogenesis.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research