Table 1.
Expression profile of the BAFF and APRIL system and clinical relevance in hematological cancers.
| Hematological Cancers | Expression Profile and Clinical Relevancy |
|---|---|
| B-ALL | Serum BAFF and APRIL concentrations are higher in B-ALL patients [114]. BAFF-R expression in primary B-ALL cases is heterogeneous (0.9% to 93% of B-ALL cells express BAFF-R) [115]. TACI and BCMA expression is relatively low to negative in B-ALL cells [115,116]. |
| HL | Increased serum levels of BAFF and APRIL in HL [117]. |
| MM | Serum levels BAFF and APRIL are three to five times higher in MM [118,119]. Higher BAFF expression is associated with disease progression and shorter progression-free survival [118,120,121,122]. BAFF-R expression is very low or absent in primary MM cells and in MM cell lines [119]. BCMA is highly expressed in the plasma cells of MM patients, and serum soluble BCMA (sBCMA) levels are used as a biomarker for MM disease status [123,124]. Patients with higher levels (above 326.4 ng/mL) of sBCMA have significantly shorter progression-free (3.6 months) and overall survival (98 months) than patients with less than 326.4 ng/mL of serum sBCMA (9.0 and 155 months, respectively) [125]. Higher TACI expression is observed in on MM cells [126,127]; however, lower TACI expression is associated with worse prognosis, including increased stage III MM probability, attenuated hemoglobin levels, and increased bone lesions [127]. |
| NHL | |
| BL | BAFF-R expression in primary BL cases is heterogeneous (0.04 to 81% of B-ALL cells express BAFF-R) [115]. |
| CLL | Increased BAFF level in CLL patients, specifically with unmutated IgHV, and increased BAFF expression is associated with worse outcomes [128,129]. The plasma level of APRIL is higher in CLL patients [128,129]. Higher intracellular APRIL and BAFF in CLL cells is associated with higher expression of adverse prognostic factors CD38 and ZAP70 and poorer clinical outcomes [128]. The expression of BAFF-R, TACI and BCMA on CLL B cells is comparable to healthy B cells [130,131,132]; however, lower BAFF-R expression on CLL B cells has also been reported [133]. CLL B cells with mutated IgHV express more TACI and BCMA than unmutated cells [132]. Plasma sBCMA levels are significantly higher in CLL patients, with the sBCMA concentration increasing with disease severity and associated with poorer outcomes [134,135]. |
| CNSL | Elevated levels of BAFF-APRIL and their receptors BCMA and TACI have been detected in the cerebrospinal fluid (CSF) and biopsies of CNSL patients, compared to patients with other neurological diseases [136,137,138]. The levels of BAFF and APRIL in CSF act as sensitive and specific biomarkers for CNSL diagnosis and therapeutic response. The serum levels of BAFF or APRIL remain unchanged, suggesting a localized response. |
| DLBCL | BAFF-R expression is comparable to healthy B cells [133]. Tumor cells also express TACI, BCMA and HSPGs [139]. Serum BAFF concentrations and APRIL expression in tumor lesions are higher and associated with poor prognosis [139,140]. |
| FL | Lower BAFF-R expression [133]. Three-fold higher serum BAFF expression compared to healthy donors [133]. |
| HCL | HCL cells express high levels of BAFF-R, TACI, BCMA, and HSPGs [141]. |
| MCL | Serum BAFF concentrations are higher and correlate to poor treatment response and relapse [142]. BAFF-R expression is comparable to healthy B cells [133]. |
| MZL | BAFF-R expression is comparable to healthy B cells [133]. |
Abbreviations: B-ALL = B-cell acute lymphoblastic leukemia; BCP = B-cell precursors; HL = Hodgkin’s lymphoma; MM = multiple myeloma; NHL = non-Hodgkin’s lymphoma; BL = Burkitt’s lymphoma; CLL = chronic lymphocytic leukemia; CNSL = central nervous system lymphoma; DLBCL = diffuse large B-cell lymphoma; FL = follicular lymphoma; HCL = hairy cell leukemia; MCL = mantle cell lymphoma; MZL = marginal zone lymphomas.