Background Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphoma. Histone deacetylase inhibitors (HDACis) have been widely applied in multiple tumours, but the expected efficacy was not observed in DLBCL. Therefore, this study is aimed to explore superior HDACis and optimise a relative combinational therapeutic strategy. Methods The antitumour effects of the drug were evaluated by Cell Counting Kit‐8 (CCK‐8) assay and apoptosis analysis. Single‐cell RNA sequencing (scRNA‐Seq) was used to analyse the intratumoural heterogeneity of DLBCL cells. Whole‐exome sequencing and RNA sequencing were performed to analyse the genetic and transcriptional features. Western blotting, qRT–PCR, protein array, immunohistochemistry, and chromatin immunoprecipitation assays were applied to explore the involved pathways. The antitumour effects of the compounds were assessed using subcutaneous xenograft tumour models. Results LAQ824 was screened and confirmed to kill DLBCL cells effectively. Using scRNA‐Seq, we characterised the heterogeneity of DLBCL cells under different drug pressures, and c‐Fos was identified as a critical factor in the survival of residual tumour cells. Moreover, we demonstrated that combinatorial treatment with LAQ824 and a c‐Fos inhibitor more potently inhibited tumour cells both in vitro and in vivo. Conclusion Altogether, we found an HDACi, LAQ824, with high efficacy in DLBCL and provided a promising HDACi‐based combination therapy strategy.

Background: Gliomas are the most refractory intracranial disease characterized by high incidence and mortality rates. Therefore, radiotherapy plays a crucial role in the treatment of gliomas. However, recent evidence reveals that ferroptosis is highly associated with radiosensitivity in tumor cells. Therefore, this study aimed to investigate radiosensitivity- and ferroptosis-associated biomarkers. Moreover, the study aimed to provide new strategies for the treatment and evaluation of prognosis in gliomas. Methods: The mRNA sequencing and relevant clinical data were obtained from The Cancer Genome Atlas (TCGA). Secondly, differential analysis was conducted to reveal the radiosensitivity- and ferroptosis-associated differentially expressed genes (DEGs). Further, a predictive model based on the seven genes was constructed, and LASSO regression analysis was carried out. After that, the Chinese Glioma Genome Atlas (CGGA) was used for validation of the results. Results: A total of 36 radiosensitivity- and 19 ferroptosis-associated DEGs with a prognostic value were identified. Moreover, seven intersecting genes (HSPB1, STAT3, CA9, MAP1LC3A, MAPK1, ZEB1, and TNFAIP3) were identified as the risk signature genes. The ROC curves and K-M analysis revealed that the signature genes showed a good survival prediction. Furthermore, the functional analysis revealed that the differentially expressed genes between the high-risk and the low-risk groups were enriched in glioma-related biological processes. In addition, differences were reported in immune function status between the two groups. Conclusion: This study revealed that the seven biomarkers could help predict the prognosis in glioma patients. In addition, this study provides a basis for understanding the molecular mechanisms of radiosensitivity and ferroptosis in the treatment of gliomas.

Glioblastoma (GBM), as the most aggressive adult brain tumor, seriously threatened people’s life with a low survival time. Standard postoperative treatment, chemotherapy combined with radiotherapy (RT), was the major therapeutic...

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BackgroundChronic lymphocytic leukemia (CLL) is a highly heterogeneous malignant lymphoproliferative B-cell disorder that can be treated using ibrutinib, a Bruton’s tyrosine kinase inhibitor. However, the ibrutinib resistance of CLL patients has caused widespread concerns, necessitating the development of novel treatment strategies. MethodsHere, we identified lectin galactoside-binding soluble 1 (LGALS1) and lymphocyte-activating gene 3 (LAG3) as potential markers for ibrutinib-resistant CLL using single-cell RNA sequencing (scRNA-seq), and the results were validated in an ibrutinib-resistant CLL cell line (MEC1-IR) and primary cells from CLL patients. Marker-gene expression was detected while functional analyses were conducted with or without OTX008, a selective Galectin-1 inhibitor. ScRNA-seq revealed that the biological features, gene expression profiles, and clonal signatures of peripheral blood mononuclear cells (PBMCs) from patients with ibrutinib-resistant CLL were distinct from those displayed by PBMCs from ibrutinib-sensitive patients.ResultsA close correlation between LGALS1 and LAG3 expression was observed and these factors were found to be highly expressed in ibrutinib-resistant CLL, with diagnostic and prognostic stratification, indicating that they may serve as drivers of ibrutinib-resistant CLL. Concordantly, LGALS1 and LAG3 expression was higher in ibrutinib-resistant CLL cells and primary cells, and OTX008 suppressed proliferation and induced apoptosis in both cells.ConclusionLGALS1 and LAG3 gene panel is promising indicator of ibrutinib-sensitivity and prognosis marker of CLL. LGALS1 inhibitor OTX008 is effective in CLL patients, both those naïve to and those resistant to ibrutinib.