Association of Common Variants of TNFSF13 and TNFRSF13B Genes with CLL Risk and Clinical Picture, as Well as Expression of Their Products—APRIL and TACI Molecules

Abstract

Interactions between APRIL (TNFSF13) and its receptor TACI (TNFRSF13B) are implicated in providing survival benefits for chronic lymphocytic leukaemia (CLL) cells. Here we explored the relationship between TNFSF13 and TNFRSF13B SNPs and expression of APRIL and TACI molecules and performed extended case-control study to evaluate earlier observations. Expression of APRIL and TACI was detected by FACS for 72 and 145 patients, respectively, and soluble APRIL was measured by ELISA in plasma of 122 patients. Genotypes were determined in 439 CLL patients and 477 control subjects with TaqMan Assays or restriction fragment length polymorphism (RFLP). The rs4968210GG genotype of TNFSF13 was associated with a lower percentage of CD19+APRIL+ cells in CLL patients when compared to (AA + GA) genotypes (p-value = 0.027). Homozygosity at rs11078355 TNFRSF13B was associated with higher CD19+ TACI+ cell percentage in CLL patients (p-value = 0.036). The analysis of extended groups of patients and healthy controls confirmed the association of TNFSF13 rs3803800AA genotype with a higher CLL risk (OR = 2.13; CI95% = 1.21; 3.75; p-value = 0.007), while the possession of TNFRSF13B rs4985726G allele (CG + GG) genotype was associated with lower risk of CLL (OR = 0.69; CI95% = 0.51; 0.95; p-value = 0.02). Genetic variants of TNFSF13 and TNFRSF13B may have an impact on APRIL and TACI expression and may be considered as possible CLL risk factors.

TNFRSF13B is a potential contributor to prostate cancer

“…A combined analysis of African and European ancestry populations identified a missense variant (rs34562254) in TNFRSF13B associated with multiple myeloma risk [50]. It has also been reported that several genetic variants in TNFRSF13B influence gene expression and susceptibility to chronic lymphocytic leukaemia [51]. Furthermore, a significant association of TNFRSF13B rs7501462 with survival was identified in a large cohort of 10,084 patients with invasive epithelial ovarian cancer [52].…”

TNFRSF13B gene mutation in familial acute myeloid leukemia: A new piece in the complex scenario of hereditary predisposition?

“…11 The higher stability of the ligand-receptor complex could physiologically produce a proliferative stimulus, favoring leukemogenesis, similarly to the phenomenon observed in the case of overexpression of TNFSF13, which may cause a higher susceptibility to CLL due to the saturation (in terms of a more significant number of interactions) of TNFRSF13B. 4 Larger data support our observations; in fact, in a recent nationwide study on cancer-prone syndromes, TNFRSF13B was reported among relevant genes associated with the childhood onset of glioma, Burkitt lymphoma and Langerhans cell histiocytosis. 3 Furthermore, as stated above, common TNFRSF13B variants and TACI expression were recently correlated with the risk of CLL onset.…”

“…3 Furthermore, common variants of TNFRSF13B and TNFSF13 (encoding APRIL, the main TACI-ligand) were recently associated with the chronic lymphocytic leukemia (CLL) risk, as well as the expression of their products (TACI and APRIL). 4 Nonetheless, the involvement of constitutive TNFRSF13B alterations in acute myeloid leukemia (AML) remains unexplored.…”

Silver nanoparticles as proapoptotic drugs: pharmacological basis in non-metastatic skin melanoma

“…13 In this sense, numerous studies have demonstrated the role of specific genes in the development of different types of cancer. [14][15][16][17][18][19] The genetic atlas of cancer is a priority for cell and molecular biology with a view to discovering the different signaling pathways involved, and identifying new targets for the development of antitumor diagnostics and drugs.…”