β-arrestin 2 (ARRB2) is involved in the desensitization and trafficking of G protein-coupled receptors (GPCRs) and plays a critical role in cell proliferation, apoptosis, chemotaxis, and immune response modulation. The role of ARRB2 in the pathogenesis of multiple myeloma (MM) has not been elucidated. This study addressed this question by evaluating the expression of ARRB2 in bone marrow (BM) samples from newly diagnosed MM patients and deriving correlations with key clinical outcomes. In light of recent trends towards the use of immune checkpoint inhibitors across malignancies, the effect of ARRB2 in the regulation of the PD-1/PD-L1 axis was also investigated. The expression of ARRB2 was significantly higher in MM patients resistant to proteosome inhibitor (bortezomib) treatment compared to those who responded. Higher ARRB2 expression in the BM of newly diagnosed MM patients was associated with inferior progression-free survival and overall survival. PD-1 expression was downregulated in CD3 T cells isolated from ARRB2 knockout (KO) mice. Furthermore, knockdown of ARRB2 with siRNA reduced PD-1 expression in murine CD3 T cells and PD-L1 expression in murine myeloid-derived suppressor cells. These findings suggest an important role of ARRB2 in MM pathogenesis, potentially mediated via modulation of immune checkpoints in the tumor microenvironment. Our study provides new evidence that ARRB2 may have non-canonical functions independent of GPCRs with relevance to the understanding of MM pathobiology as well as immunotherapy and checkpoint inhibitor escape/resistance more broadly.

Mature B-cell non-Hodgkin lymphoma (B-NHL) is a prevalent pediatric malignancy with significant treatment advancements. This study retrospectively analyzes clinical characteristics, treatment outcomes, and survival rates of children and adolescents diagnosed with B-NHL at Al-Hasan Al-Mojtaba Hospital between January 2014 and December 2024. A comparative analysis was performed between the LMB96 and R-CHOP regimens. Patients with confirmed diagnoses of Large B-cell lymphoma or Burkitt’s lymphoma, based on WHO classification criteria, were included. Staging was conducted using the St. Jude system, and risk classification followed the FAB/LMB criteria. Treatment involved a modified LMB96 regimen, later replaced by R-CHOP in the last two years of the study. Event-free survival (EFS) was analyzed using Kaplan-Meier survival curves, with stratifications by staging, risk group, and gender. A total of 66 patients were included (median age: 5.8 years; 69.7 % male). Burkitt’s lymphoma was the predominant histology (86.3 %). The abdomen was the most common primary site (84.8 %). The majority of patients (72.7 %) presented with advanced-stage disease (Stages III and IV). Risk group classification identified 62.1 % of patients in Group B and 28.8 % in Group C. Kaplan-Meier survival analysis revealed Group A had the most favorable prognosis (EFS ∼100 %), followed by Group B (∼75 %), and Group C (∼50 %). Disease stage significantly influenced survival (p = 0.021), with Stage IV patients demonstrating the poorest outcomes. While female patients exhibited higher EFS than males, the difference was not statistically significant (p = 0.27). By the end of follow-up, 28.8 % of patients had experienced a fatal outcome. Advanced-stage B-NHL remains prevalent, with significant survival differences based on staging and risk classification. The transition from LMB96 to R-CHOP warrants further evaluation to optimize pediatric treatment strategies. Larger studies are needed to validate observed gender-based survival trends.

Beta-arrestin 1 (ARRB1) is a multifunctional adaptor protein that regulates diverse signaling pathways beyond its canonical role in G-protein-coupled receptor desensitization. While ARRB1 has been implicated in cancer progression, its role in modulating host immunity against multiple myeloma (MM) remains unexplored. Here, we demonstrate that host ARRB1 deficiency significantly enhances anti-myeloma immunity and prolongs survival in a syngeneic murine MM model. Using Vk*MYC myeloma cells transplanted into wild-type and ARRB1 knockout mice, we show that ARRB1 deficiency in the host microenvironment promotes robust T cell infiltration and activation while reducing immunosuppressive myeloid populations. Notably, ARRB1 knockout mice exhibited markedly decreased programmed cell death protein-1 (PD-1) expression on both T cells and myeloid-derived suppressor cells, indicating reduced immune exhaustion. Furthermore, ARRB1 deficiency conferred protection against myeloma-induced bone disease, suggesting a dual role in immune regulation and bone homeostasis. These findings establish ARRB1 as a critical negative regulator of host anti-myeloma immunity and identify it as a potential therapeutic target for enhancing immunotherapy efficacy in MM.