MT-2

Melphalan Improves Toxicity of Arsenic Trioxide in Adult T-cell Leukemia/Lymphoma Cells

Adult T-cell leukemia/lymphoma (ATLL) is a hematologic neoplasm with poor prognosis. Melphalan is an alkylating anti-cancer agent, and arsenic trioxide (ATO) is routine chemotherapy drug for ATLL with low response rate. Due to the significant challenge that chemoresistance poses in treating ATLL, we aimed to investigate the potential of melphalan to enhance the effects of ATO as a combinatorial treatment approach for ATLL.

MT-2 cells were exposed to different concentrations of melphalan and ATO and viability was evaluated by alamarBlue assay. Upon IC₅₀ determination, cells were treated with 0.5 μg/ml melphalan and 2 μM ATO for 72 h, and changes induced on the cell cycle were analyzed by PI staining and flow cytometry, while the expression of candidate genes was assessed by quantitative PCR.

Fig. 1. Viability of MT-2 cells after 72 h treatment with melphalan and ATO, alone and in combination (A). Flow cytometry histograms (B) and quantitative analysis (C) of the cell cycle upon single and combinatorial use of melphalan and ATO (Khodadadi, Faeze, et al. 2025).

RELA/C Knockout Reduced FOXP3 Expression and Immune-suppressive Function of Tregs.

Mutations in NF-κB-related molecules result in combined immunodeficiency characterized by recurrent infection. This study aimed to investigate the association between mutations in NF-κB family members (RELA, RELB, and RELC) and regulatory T cell (Treg) function in humans. Similar to that observed in knockout mice, RELA or RELC knockout in MT-2 cells and freshly isolated Tregs reduced FOXP3 expression and the immune suppressive function of Tregs. Additionally, PD-L1 expression in effector T cells and Tregs decreased considerably following RELC knockdown. These findings demonstrated that the deletion of RELA or RELC resulted in the loss of Treg-like phenotype and function owing to the downregulation of FOXP3 expression.

Fig. 2. FOXP3 expression was partially lost in MT-2 cells bearing RELA and RELC knockout (Sato, Yohei, Yamato Hanawa, and Akihito Tsubota. 2024).