Role of BAFF and APRIL in human B‐cell chronic lymphocytic leukaemia

Abstract

SummaryB-cell chronic lymphocytic leukaemia (B-CLL) is the most prevalent leukaemia in Western countries and is characterized by the gradual accumulation in patients of small mature B cells. Since the vast majority of tumoral cells are quiescent, the accumulation mostly results from deficient apoptosis rather than from acute proliferation. Although the phenomenon is relevant in vivo, B-CLL cells die rapidly in vitro as a consequence of apoptosis, suggesting a lack of essential growth factors in the culture medium. Indeed, the rate of B-CLL cell death in vitro is modulated by different cytokines, some favouring the apoptotic process, others counteracting it. Two related members of the tumour necrosis factor family, BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferationinducing ligand), already known for their crucial role in normal B-cell survival, differentiation and apoptosis, were recently shown to be expressed by B-CLL cells. These molecules are able to protect the leukaemic cells against spontaneous and drug-induced apoptosis via autocrine and/or paracrine pathways. This review will focus on the role of BAFF and APRIL in the survival of tumoral cells. It will discuss the expression of these molecules by B-CLL cells, their regulation, transduction pathways and their effects on leukaemic cells. The design of reagents able to counteract the effects of these molecules seems to be a new promising therapeutic approach for B-CLL and is already currently developed in the treatment of autoimmune diseases.

Transcriptomic analyses of genes differentially expressed by high-risk and low-risk human papilloma virus E6 oncoproteins

“…CYP1B1 is a metabolic enzyme involved in degradation of environmental carcinogens like benzo(a)-pyrene and other polycyclic hydrocarbons (PAHs) present in environmental pollution and cigarette smoke which forms DNA adducts [22], and converts them to soluble products which are excreted out. Elevated CYP1B1 expression may result in a greater load of reactive oxygen intermediates (ROMs) causing genotoxic stress and tumour initiation [12,37]. There has been no report on the role of LAMA2 in cancer development; however from our studies we have observed a downregulation of LAMA2 expression.…”

Role of miR-15/16 in CLL

“…APRIL and BAFF are two members of the TNF superfamily and show abnormally high expression levels in a number of B-cell malignancies, including mantle cell lymphoma, diffuse large cell lymphoma, and CLL. 39 APRIL binds to two of its receptors, TACI and BCMA (B-cell maturation antigen). 39 TACI and BCMA interact with various TRAF family members and activate the NF-kB pathway.…”

“…39 APRIL binds to two of its receptors, TACI and BCMA (B-cell maturation antigen). 39 TACI and BCMA interact with various TRAF family members and activate the NF-kB pathway. 39 Thus, NF-kB activation through TACI and BCMA may be an important pathway and is important in CLL pathogenesis.…”

“…39 TACI and BCMA interact with various TRAF family members and activate the NF-kB pathway. 39 Thus, NF-kB activation through TACI and BCMA may be an important pathway and is important in CLL pathogenesis. 37 We investigated whether DLEU7 expression has an effect on NF-kB activation by TACI and BCMA.…”

Evaluation of TNF superfamily molecules release by neutrophils and B leukemic cells of patients with chronic B – cell lymphocytic leukemia

“…According to various authors' studies, BAFF and APRIL molecules control homeostasis of B lymphocytes, their differentiation, maturation and survival in the physiological and pathological states, including neoplasms. It was proved that the increased expression of these molecules induced the development of B cells in chronic B-cell lymphocytic leukemia (B-CLL) [4,5]. TRAIL molecule was also found to play a role in the survival of B cells in B-CLL [6].…”