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Tumour microenvironment harbours diverse stress factors that affect the progression of multiple myeloma (MM), and the survival of MM cells heavily relies on crucial stress pathways. However, the impact of cellular stress on clinical prognosis of MM patients remains largely unknown. This study aimed to provide a cell stress‐related model for survival and treatment prediction in MM. We incorporated five cell stress patterns including heat, oxidative, hypoxic, genotoxic, and endoplasmic reticulum stresses, to develop a comprehensive cellular stress index (CSI). Then we systematically analysed the effects of CSI on survival outcomes, clinical characteristics, immune microenvironment, and treatment sensitivity in MM. Molecular subtypes were identified using consensus clustering analysis based on CSI gene profiles. Moreover, a prognostic nomogram incorporating CSI was constructed and validated to aid in personalised risk stratification. After screening from five stress models, a CSI signature containing nine genes was established by Cox regression analyses and validated in three independent datasets. High CSI was significantly correlated with cell division pathways and poor clinical prognosis. Two distinct MM subtypes were identified through unsupervised clustering, showing significant differences in prognostic outcomes. The nomogram that combined CSI with clinical features exhibited good predictive performances in both training and validation cohorts. Meanwhile, CSI was closely associated with immune cell infiltration level and immune checkpoint gene expression. Therapeutically, patients with high CSI were more sensitive to bortezomib and antimitotic agents, while their response to immunotherapy was less favourable. Furthermore, in vitro experiments using cell lines and clinical samples verified the expression and function of key genes from CSI. The CSI signature could be a clinically applicable indicator of disease evaluation, demonstrating potential in predicting prognosis and guiding therapy for patients with MM. [ABSTRACT FROM AUTHOR]

Background: Lysine methyltransferase 2D (KMT2D) mediates mono‐methylation of histone H3 lysine 4 (H3K4me1) in mammals. H3K4me1 mark is involved in establishing an active chromatin structure to promote gene transcription. However, the precise molecular mechanism underlying the KMT2D‐mediated H3K4me1 mark modulates gene expression in triple‐negative breast cancer (TNBC) progression is unresolved. Methods and Results: We recognized Y‐box‐binding protein 1 (YBX1) as a "reader" of the H3K4me1 mark, and a point mutation of YBX1 (E121A) disrupted this interaction. We found that KMT2D and YBX1 cooperatively promoted cell growth and metastasis of TNBC cells in vitro and in vivo. The expression levels of KMT2D and YBX1 were both upregulated in tumour tissues and correlated with poor prognosis for breast cancer patients. Combined analyses of ChIP‐seq and RNA‐seq data indicated that YBX1 was co‐localized with KMT2D‐mediated H3K4me1 in the promoter regions of c‐Myc and SENP1, thereby activating their expressions in TNBC cells. Moreover, we demonstrated that YBX1 activated the expressions of c‐Myc and SENP1 in a KMT2D‐dependent manner. Conclusion: Our results suggest that KMT2D‐mediated H3K4me1 recruits YBX1 to facilitate TNBC progression through epigenetic activation of c‐Myc and SENP1. These results together unveil a crucial interplay between histone mark and gene regulation in TNBC progression, thus providing novel insights into targeting the KMT2D‐H3K4me1‐YBX1 axis for TNBC treatment. Highlights: YBX1 is a KMT2D‐mediated H3K4me1‐binding effector protein and mutation of YBX1 (E121A) disrupts its binding to H3K4me1.KMT2D and YBX1 cooperatively promote TNBC proliferation and metastasis by activating c‐Myc and SENP1 expression in vitro and in vivo.YBX1 is colocalized with H3K4me1 in the c‐Myc and SENP1 promoter regions in TNBC cells and increased YBX1 expression predicts a poor prognosis in breast cancer patients. [ABSTRACT FROM AUTHOR]

Mono‐methylation of histone H3 on Lys 4 (H3K4me1), which is catalyzed by histone‐lysine N‐methyltransferase 2D (KMT2D), serves as an important epigenetic regulator in transcriptional control. In this study, the authors identify early B‐cell factor 2 (EBF2) as a binding protein of H3K4me1. Combining analyses of RNA‐seq and ChIP‐seq data, the authors further identify killin (KLLN) as a transcriptional target of KMT2D and EBF2 in pancreatic ductal adenocarcinoma (PDAC) cells. KMT2D‐dependent H3K4me1 and EBF2 are predominantly over‐lapped proximal to the transcription start site (TSS) of KLLN gene. Comprehensive functional assays show that KMT2D and EBF2 cooperatively inhibit PDAC cells proliferation, migration, and invasion through upregulating KLLN. Such inhibition on PDAC progression is also achieved through increasing H3K4me1 level by GSK‐LSD1, a selective inhibitor of lysine‐specific demethylase 1 (LSD1). Taken together, these findings reveal a new mechanism underlying PDAC progression and provide potential therapeutic targets for PDAC treatment. [ABSTRACT FROM AUTHOR]

Background: Plasma cell mastitis (PCM), also known as mammary duct ectasia, is a chronic nonbacterial breast inflammation characterized by duct expansion and plasma cell infiltration. The severe and intense clinical manifestations profoundly affect the quality of life of female patients. Although the pathological process of PCM is known to include four stages (duct dilatation, inflammation, abscess and fistula), there is still lack of imaging techniques and serum markers with high specificity in clinical practice. Due to recurrent acute attacks and the prolonged healing process of the disease, most patients choose to accept mastectomy. Summary: We searched for studies, reports and reviews referring to PCM in the past 20 years; more than half of the results were related to animal studies, and little attention has been paid to human beings, which may explain the frequent misdiagnosis of PCM as breast cancer and the limited treatment options. This review focuses on the current diagnostic methods and markers for PCM and hierarchically discusses the typical clinical features, etiological causes and relevant molecular mechanisms of PCM. Key Messages: We herein highlight the urgent need to develop more specific and sensitive biomarkers in the clinical laboratory. It will help to establish a standardized flowchart for the diagnosis and treatment of PCM in order to improve recovery for female patients. [ABSTRACT FROM AUTHOR]