REL (REL Proto-Oncogene)

Moreover, upon ibrutinib treatment, REL DNA-binding activity decreased in 2pWT CLL cells but remained sustained in 2p+ CLL cells following BCR stimulation, suggesting that persistent NF-κB activation contributes to resistance...Altogether, our study identifies REL overexpression as a novel 2p+-driven mechanism of BTKi resistance in CLL, complementing the well described BTK and PLCG2 mutations. These findings support the clinical relevance of detecting 2p gain to guide treatment strategies and improve outcomes in CLL.

This study establishes ABCs and NF-κB/c-Rel signaling as central contributors to AChR-MG immunopathology. Therefore, ABCs may serve as complementary biomarkers for clinical stratification.

Ighv dominance was increased at the mRNA level in RELoverexpressing B-cells and clonal expansion was detected at the DNA level in some cases. Highlighting the role of the immune response, our results demonstrate the advantage conferred by REL in the GC competition and provide evidence that, as an oncogenic event of GC B-cells, its genetic deregulation induces the generation of a long-term pool of lymphoma precursor cells.

Significantly reduced tumor growth was observed in mice treated with the c-Rel siRNA nanoparticles compared to control mice. Our data indicates that peptide-based nanoparticles can be successfully utilized to target the myeloid immune checkpoint c-Rel for the treatment of cancer.

These subgroups were more sensitive to Sunitinib and CTLA4 blockade...TAGAP's effects on CD4+ T cells were partly reversed by c-Rel overexpression, highlighting TAGAP's role in rejuvenating CD4+ T cells and exerting anticancer effects by inhibiting c-Rel. This study elucidates the novel therapeutic potential of targeting TAGAP to modulate CD4+ T cell activity in immunotherapy for LUSC.

Different IMiDs are currently used in clinical practice in combination with PI, such as Lenalidomide (LEN) and Pomalidomide (POM), having both cereblon as the main target...Aims: This project's focus was to evaluate the molecular mechanism of resistance to IMiDs resistance, namely LEN and POM, in MM cells and assess the cross-resistance to Bortezomib (BTZ)... The resistant models developed show different degrees of resistance according to IMiD and cell line. In LEN- resistant models, H929-RL and U-266RL cells presented an IC 25 6.5x and over 1000x higher compared to parental cells, respectively. The U-266RP cells showed an IC 25 500x higher than U-266 cells.

Patients with PD-L1 gene amplification, PD-L1+ tumor cells, and high mRNA levels of CD3D, HLA-DRA, and LAG3 in baseline tumor tissue may be more responsive to zanubrutinib and tislelizumab combination therapy. A high mRNA level of REL or mutations in TP53 may contribute to resistance of zanubrutinib and tislelizumab combination therapy. Due to the limited number of samples, results must be interpreted with caution.