Protein arginine methyltransferase 1 (PRMT1) serves as a crucial regulator of post-translational modifications of proteins. While PRMT1 has been implicated in the progression of various cancers, its specific role in chronic lymphocytic leukemia (CLL) remains to be fully elucidated. This study aimed to investigate the oncogenic function of PRMT1 and assess the therapeutic efficacy of a selective PRMT1 inhibitor, C7280948, in CLL. Elevated expression of PRMT1 was observed in CLL cells and was associated with unfavorable prognosis. Additionally, in vitro and in vivo experiments demonstrated that treatment with C7280948 effectively inhibited tumor growth in CLL. Quantitative proteomics and co-immunoprecipitation analyses revealed an interaction between PRMT1 and MAST1, which was found to facilitate CLL progression. PRMT1 inhibition decreased the asymmetric dimethylarginine of MAST1 at R806 and downregulated the activation of the MAPK pathway by affecting the phosphorylation of MEK1 and ERK1/2 in CLL cells. In summary, our results indicated that PRMT1 promoted CLL tumorigenesis via MAST1-mediated regulation of MEK1 signaling and highlighted the potential of C7280948 as a novel therapeutic agent for CLL treatment.

Chimeric antigen receptor (CAR)-T cell therapy has demonstrated remarkable efficacy in treating hematological malignancies. However, this approach faces substantial limitations, including protracted manufacturing periods, elevated costs, restricted patient eligibility attributable to manufacturing constraints, and intolerate lymphodepleting preconditioning regimens. To address these challenges, in vivo CAR-T cell therapy has emerged as a promising alternative, directly engineering immune cells within the patient through targeted delivery systems such as engineered viral vectors, lipid nanoparticles, and other non-viral platforms. This approach offers immediate administration and enhanced scalability compared with ex vivo methods. The 2025 American Society of Hematology annual meeting presented multiple abstracts advancing this field, with this review focusing on studies demonstrating novel delivery system innovations, including engineered lentiviral vectors and non-viral platforms, as well as expanded therapeutic applications beyond oncology to autoimmune diseases. By integrating these conference presentations with recent peer-reviewed literature, this paper summarizes the current landscapes of in vivo CAR-T cell therapy presented at the conference.

Biomedical research data visualization faces several challenges, including insufficient expertise and fragmented methodologies, which severely limit research efficiency and result quality. FigureYa is a standardized visualization framework composed of 317 modular R/python scripts, rather than a standalone software or desktop application. It covers key domains such as expression profiling, immune analysis, survival analysis, and single-cell data visualization. Based on the concept of “replace data and use,” FigureYa significantly lowers the technical threshold, allowing researchers to generate high-quality charts without requiring an extensive programming background. Compared to generic online R code snippets, FigureYa offers rigorously developed, thoroughly validated, and biologically contextualized visualization modules originally written by the author team. Each script includes version-matched environments, example datasets, and detailed annotations, providing clear advantages in automation, reproducibility, and scientific professionalism, thereby providing a standardized visualization solution for complex biomedical data. This innovative tool optimizes research time allocation, promotes interdisciplinary collaboration, accelerates scientific discovery and clinical translation, and provides robust data visualization support for biomedical research.

Background: Bruton's tyrosine kinase (BTK), a pivotal regulator of B-cell receptor (BCR) signaling, plays a critical role in the survival, proliferation, and migration of malignant B cells. Orelabrutinib, a novel, highly selective and irreversible BTK inhibitors, has emerged as a promising candidate for the treatment of B-cell lymphoma. This study was conducted to evaluate the preliminary efficacy and safety of Orelabrutinib-based regimens for marginal zone lymphoma (MZL) patients. Methods: This was a retrospective real-world study in patients with clinical and histopathological confirmed MZL in China. We retrospectively investigated the clinical information and treatment outcome of 38 MZL patients between 2022 and 2025. Results: 38 MZL patients were enrolled in the study. Among them, 17 patients (44.7%) received orelabrutinib-based regimens, with the median treatment duration of 4 months (range, 1 - 13 months). The median age was 66 years (range, 52 - 81 years), with 9 males (52.9%). There were 12 cases (70.6%) of extranodal MZL (involving the breast, stomach, kidney, bone marrow, chest wall, etc.), 3 cases (17.6%) of nodal MZL, and 2 cases (11.8%) of splenic MZL. Moreover, 10 patients (58.8%) had an ECOG score of 0–1, 6 patients (35.3%) had B symptoms, 11 cases (64.7%) were Ann Arbor stage III–IV, 15 cases (88.2%) had an MZL International Prognostic Index (MZL-IPI) score of 1–2, and 6 cases (35.3%) had bone marrow involvement. In the total of 38 MZL patients, 22 cases had evaluable response evaluation. MZL patients in the orelabrutinib-based regimens group (n=9) did not have a superior overall response rate (ORR) compared with control group [77.8% (7/9) vs. 76.9% (10/13)]. Interestingly, MZL patients received orelabrutinib-based regimens achieved a significantly higher complete response rate (CRR) [66.7% (6/9) vs. 15.4% (2/13)]. Notably, all 7 patients who received orelabrutinib maintenance therapy achieved an ORR of 100%, whereas the 2 patients without orelabrutinib maintenance therapy had an ORR of 0%. In the orelabrutinib–based regimens group (n=17), none of the remaining 8 MZL patients experienced disease progression, yielding an overall disease control rate (DCR) of 94.1% (16/17). With a median follow-up of 343 days (range, 36–1166 days), neither median overall survival (OS) nor progression-free survival (PFS) was reached. Moreover, no grade ≥3 adverse events were observed in the study. Conclusions: Our preliminary results suggested that orelabrutinib-based regimens may be a well-tolerated and effective regimen in MZL patients. Future studies with a large sample size and longer follow-up time are needed to validate the conclusion.

BACKGROUND:Fatty acids serve as a crucial energy source for tumor cells during the progression of chronic lymphocytic leukemia (CLL). The present study aims to elucidate the characteristics of fatty acid metabolism (FAM) in CLL, construct a related prognostic score, and investigate the regulatory role and mechanisms of FAM in CLL development. METHODS:Bulk RNA sequencing data from CLL patients and healthy controls were analyzed to identify differentially expressed fatty acid metabolic genes. FAM-score was constructed using Cox-LASSO regression and validated. Single-cell RNA sequencing was used to analyze the expression of key FAM genes in CLL immune cell subsets and investigate cellular communication. Functional assays, including cell viability, drug sensitivity, and oxygen consumption assays, were performed to assess the impact of fatty acid oxidation (FAO) inhibition on CLL cells. RESULTS:Three FAM-related genes (LPL, SOCS3, CNR1) were identified with independent prognostic significance to construct the risk score. The FAM-score demonstrated superior prognostic performance compared to the Binet stage and was associated with established clinical prognostic markers. Single-cell analysis revealed distinct expression patterns of LPL, SOCS3, and CNR1 across CLL immune cell subsets. Cellular communication analysis highlighted the regulatory role of distinct B cell and Treg subsets in the CLL microenvironment. CLL patients with high FAM-score displayed distinct immune infiltration patterns, with increased FAO pathway activity. Inhibition of FAO reduced CLL cell viability, synergistically enhanced the efficacy of the PI3K inhibitor idelalisib. CONCLUSION:The present study constructed a prognostic risk score based on FAM gene expression, revealing related immune phenotypic differences and exploring the regulatory role of FAO in CLL development. Targeting fatty acid metabolism potentially modulates the CLL immune microenvironment and synergistically enhances the efficacy of PI3K inhibitors.

Chronic lymphocytic leukemia (CLL) is characterized as a clonal proliferation of mature B lymphocytes with distinct immunophenotypic traits, predominantly affecting the middle-aged and elderly population. This condition is marked by an accumulation of lymphocytes within the peripheral blood, bone marrow, spleen, and lymph nodes. The associated immune dysregulation predisposes CLL patients to a higher risk of secondary malignancies and infections, which significantly contribute to morbidity and mortality rates. The advent of immunotherapy has revolutionized the prognosis of CLL, advancing treatment modalities and offering substantial benefits to patient outcomes. This review endeavors to synthesize and scrutinize the efficacy, merits, and limitations of the current immunotherapeutic strategies for CLL. The aim is to inform the selection of optimal treatment regimens tailored to individual patient needs. Furthermore, the review juxtaposes various therapeutic combinations to elucidate the comparative advantages of each approach, with the ultimate objective of enhancing patient prognosis and quality of life.

Background: Acquired hemophilia A (AHA) is a rare bleeding disorder in which inhibitory antibodies neutralize factor VIII (FVIII) activity, leading to high morbidity and mortality. Although the standard of care is immunosuppressive treatment (IST) to eradicate inhibitors, there are no specific guidelines for the best immunosuppressive regimen, especially for relapsing patients. Recently, the reported upfront combined CyDRi regimen from Hungary has produced markedly higher complete remission (CR) rates and overall survival (OS) than currently used sequential regimens for newly diagnosed patients. This retrospective study aimed to investigate the efficacy and safety of RCD pulse regimen (similar to the CyDRi ) for AHA. Methods: From October 2024 to July 2025, a total of 8 patients with AHA (including 4 relapsed patients and 4 newly diagnosed patients) in our center were enrolled in this study, and received at least 1 course of RCD. The RCD pulse regimen is a combined immunosuppressive therapy (IST) consisting of: 500mg cyclophosphamide intravenously on days 1, 8, 15, and 22; 40mg dexamethasone, intravenously or orally, on days 1, 8, 15, and 22; and 100mg rituximab intravenously on days 1, 8, 15, and 22. When necessary, RCD was repeated no earlier than day 43 of the previous cycle if a complete response (CR) was not achieved. All patients received infection prophylaxis with sulfamethoxazole and trimethoprim (480 mg once daily) and acyclovir (400 mg once daily). Ethical approval and informed consent were obtained for this study. Results: Among the 8 included patients, 6 were male and 2 were female, with ages ranging from 31 to 90 years old. The median time from the first symptom to diagnosis was 2 months (range, 1 - 12 months). Comorbidities included nephrotic syndrome, hemorrhoids, diabetes mellitus, breast cancer, arrhythmia, headache, cardiac pacemaker implantation, prostatic hyperplasia, bilateral renal cysts, knee arthritis, osteoporosis, cataract, hypertension, coronary heart disease, depression, and interstitial pneumonia. An underlying disease was identified in 2 patients (25%), both with interstitial pneumonia, and one of them also had unclassified rheumatism; the remaining 6 cases (75%) were considered idiopathic. Except for 1 patient without bleeding manifestations, the other 7 cases all had skin ecchymoses, 4 had muscle hematomas, 2 had joint bleeding, and 1 had recurrent upper gastrointestinal bleeding. Of the 8 patients, 4 (50%) presented with active bleeding requiring bypassing agents (administered concurrently with the RCD regimen) from admission until bleeding was controlled. The remaining 4 patients had a recent history of bleeding but were not actively bleeding at admission and received RCD without concurrent bypassing agents. The median time for bleeding control after RCD treatment was 1.5 weeks (range, 0 - 3 weeks). The median value of FVIII activity at diagnosis was 1.8 IU/dL (range, 0.1 - 2.6 IU/dL), and the median initial inhibitor titer was 48.65 BU (range, 7.5 - 131 BU). Among the 8 patients, 6 (75%) had initial Bethesda titers > 20 BU, while 5 (62.5%) had initial Bethesda titers > 20 BU before receiving RCD treatment. Two patients with inhibitors > 100 BU and 2 patients with inhibitors < 20 BU did not achieve CR after prednisolone alone or combination therapy with the addition of cyclophosphamide prior to RCD. To date, 7 of the 8 (87.5%) patients have achieved CR after 1 or 2 courses of RCD (3 newly diagnosed patients after 1 courses of RCD, 1 newly diagnosed patient and 3 relapsed patients after 2 courses of RCD). One patient who relapsed after 313 weeks of treatment with prednisone and other drugs cannot be treated strictly in accordance with the protocol of this study, and has not achieved CR so far after 1.5 courses of RCD within 12 weeks. The median follow-up for patients with CR was 9 weeks (range, 1 44 weeks). During RCD treatment, 1 patient expernced asymptomatic lymphocytopenia (Grade 1 AE), and another developed bacterial pneumonia (Grade 2 AE), which was rapidly controlled with antibiotics without affecting IST. Conclusion: This study demonstrates that the pulse RCD regimen is effective with low toxicity for AHA (including relapsing and newly diagnosed patients), which should be considered as an attractive treatment option. However, more studies and longer follow-up periods are still needed to verify the efficacy and safety of this regimen.

Introduction: Chronic lymphocytic leukemia (CLL) progression might be subject to fatty acid metabolic reprogramming. However, precisely how fatty acid metabolism (FAM) is involved in CLL pathogenesis is elusive. The present study elucidated the transcriptomic signatures of FAM, which indicate differences in prognosis and immune function, and investigated the metabolism-dependent sensitivity to PI3K inhibitor in CLL. Methods: The prognostic model FAM-Score based on fatty acid metabolic genes was constructed in the training cohort of 487 CLL patients by Cox-LASSO regression analyses and validated in the independent cohort of 195 CLL patients. The samples were analyzed using the ssGSEA and CIBERSORT algorithms to define the immunometabolism landscape of CLL patients. Moreover, the reciprocal molecules of the FAM-related genes were identified from single-cell RNA sequencing analysis of CLL patients. Functional enrichment analysis was performed using the Gene Ontology (GO) database. CCK-8 was used to detect cell viability treated with PI3K inhibitor idelalisib following inhibition of fatty acid oxidation. Results: The fatty acid metabolic genes LPL, SOCS3, and CNR1 with independent prognostic significance were selected from 864 differentially expressed genes to construct the FAM-Score. The ROC analysis showed better specificity and sensitivity of FAM-Score (AUC = 0.738, p < 0.001) than Binet stage (AUC = 0.527, p = 0.487). The Kaplan-Meier curves suggested a significant association between high-risk subgroup and undesirable overall survival in CLL patients (p < 0.001). To further investigate the role of the FAM-Score in the CLL immune microenvironment, the abundance of immune cells between the two subgroups was quantified for comparison. The results showed significant differences in T cells, NK cells, and macrophages, suggesting the impact of FAM in CLL immunophenotype. Consistently, the expression of LPL, SOCS3, and CNR1 showed evident immune cell subset specificity at the single-cell level in CLL patients. To investigate the mechanism of FAM-induced differences in CLL immunophenotype, the reciprocal molecules of the key genes were identified. The results of functional analysis demonstrated that the interacting genes are enriched in the immune cell activation pathway and its regulatory pathways. Moreover, the fatty acid oxidation pathway, in which the differentially expressed genes of patients with higher FAM-Score were notably enriched, was significantly more active in CLL patients than in healthy controls at the single-cell level. Therefore, CLL cells were treated with the fatty acid oxidation inhibitor perhexiline, which demonstrated that the inhibition of fatty acid oxidation impeded the survival of CLL cells and enhanced their sensitivity to PI3K inhibitor idelalisib. Conclusions: The present study identified a robust clinical prognostic score based on fatty acid metabolic genes and revealed the immunophenotypic differences in CLL related to FAM-Score. Inhibiting fatty acid oxidation in CLL cells enhances the therapeutic efficacy of the PI3K inhibitor and suppresses cell proliferation activity. Although the specific mechanisms of FAM underlying CLL progression are not fully clarified, FAM pathways represent a promising avenue for amplifying the therapeutic strategies against CLL.

BackgroundDisorders of lipid metabolism are critical factors in the progression of chronic lymphocytic leukemia (CLL). However, the characteristics of lipid metabolism and related regulatory mechanisms of CLL remain unclear.MethodsHence, we identified altered metabolites and aberrant lipid metabolism pathways in patients with CLL by ultra-high-performance liquid chromatography-mass spectrometry-based non-targeted lipidomics. A combination of transcriptomics and lipidomics was used to mine relevant target molecule and downstream signaling pathway. In vitro cellular assays, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, fluorescent staining, RNA sequencing, and coimmunoprecipitation were used to monitor the molecular levels as well as to explore the underlying mechanisms.ResultsSignificant differences in the content of 52 lipid species were identified in CLL samples and healthy controls. Functional analysis revealed that alterations in glycerolipid metabolism, glycerophospholipid metabolism, sphingolipid metabolism, and metabolic pathways had the greatest impact on CLL. On the basis of the area under the curve value, a combination of three metabolites (phosphatidylcholine O-24:2_18:2, phosphatidylcholine O-35:3, and lysophosphatidylcholine 34:3) potentially served as a biomarker for the diagnosis of CLL. Furthermore, utilizing integrated lipidomic, transcriptomic, and molecular studies, we reveal that ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) plays a crucial role in regulating oncogenic lipogenesis. ENPP2 expression was significantly elevated in patients with CLL compared with normal cells and was validated in an independent cohort. Moreover, ENPP2 knockdown and targeted inhibitor PF-8380 treatment exerted an antitumor effect by regulating cell viability, proliferation, apoptosis, cell cycle, and enhanced the drug sensitivity to ibrutinib. Mechanistically, ENPP2 inhibited AMP-activated protein kinase (AMPK) phosphorylation and promoted lipogenesis through the sterol regulatory element-binding transcription factor 1 (SREBP-1)/fatty acid synthase (FAS) signaling pathway to promote lipogenesis.ConclusionsTaken together, our findings unravel the lipid metabolism characteristics of CLL. Moreover, we demonstrate a previously unidentified role and mechanism of ENPP2 in regulation of lipid metabolism, providing a novel therapeutic target for CLL treatment.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with alterations in genetic expression and epigenetic modifications. In recent years, the new insight into epigenetics in the pathogenesis of CLL has been developed considerably, including DNA methylation, histone modification, RNA methylation, non-coding RNAs as well as chromatin remodeling. Epigenetic modification regulates various processes such as stem cell biology, cell growth, and tumorigenesis without altering gene sequence. Growing evidence indicates that the disturbance of gene expression profiles which were regulated by epigenetic modifications exerts vital roles in the development and progress in CLL, which provides novel perspectives to explore the etiology of CLL. In addition, the integration with epigenetic therapeutic targets and the in-depth understanding of epigenetic therapy contribute to develop new therapeutic strategies for CLL. Herein, the present review discusses the advances of epigenetic alterations in the pathogenesis, diagnosis, and prognostic assessment of CLL patients and also highlights existing and emerging agents targeting epigenetic regulators.

In the past decade, digitization of medical records and multiomics data analysis in lymphoma has led to the accessibility of high-dimensional records. The digitization of medical records, the visualization of extensive volume data extracted from medical images, and the integration of multiomics methods into clinical decision-making have produced many datasets. As a promising auxiliary tool, machine learning (ML) intends to extract homologous features in large-scale data sets and encode them into various patterns to complete complicated tasks. At present, artificial intelligence and digital mining have shown promising prospects in the field of lymphoma pathological image analysis. The paradigm shift from qualitative analysis to quantitative analysis makes the pathological diagnosis more intelligent and the results more accurate and objective. ML can promote accurate lymphoma diagnosis and provide patients with prognostic information and more individualized treatment options. Based on the above, this comprehensive review of the general workflow of ML highlights recent advances in ML techniques in the diagnosis, treatment, and prognosis of lymphoma, and clarifies the boundedness and future orientation of the ML technique in the clinical practice of lymphoma.

Studies have indicated cancer-associated fibroblasts (CAFs) could have a significant impact in gastric cancer (GC) progression and chemotherapy resistance. However, the gene related to cancer fibroblasts that can be used as biomarkers to judge the occurrence of gastric cancer has not been fully explored. Based on two Gene Expression Omnibus (GEO) datasets, we focus on differentially expressed genes which may act as CAFs markers related to GC. Through COX regression, LASSO regression and Kaplan-Meier survival analysis, we discovered three upregulated genes (GLT8D2, GNAS and EDA) associated with poor GC patients’ survival. By single-cell analysis and nomogram, we found that EDA may affect fibroblast production and disease prognosis in GC patients. EDA expression showed a positive correlation with 5-Fluorouracil IC50 values. Immunohistochemistry (IHC) and real time PCR indicated elevated EDA levels in GC tissues and cells. Enrichment analysis revealed that EDA was closely linked to immune system regulation. IHC and single-cell analysis indicated that EDA gene was associated with cancer fibroblasts marker FGF12 and influence cell interferon-gamma response, which may play a role in regulating immune-related characteristics. In summary, we concluded that EDA may be used as a new therapeutic CAFs marker for GC.

Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin lymphoma with highly heterogeneous clinical courses. Paired-box 5 (PAX5), the regulator of B cell differentiation and growth, is abnormally expressed in several types of cancers. Herein, we explored the prognostic value of PAX5 in MCL by comprehensively analyzing the clinical features and laboratory data of 82 MCL cases. PAX5 positivity was associated with shorter overall survival (OS; p = 0.011) and was identified as an independent prognostic factor in MCL patients. The elevated β2-MG (p = 0.027) and advanced Mantle Cell Lymphoma International Prognostic Index (MIPI) score (p = 0.014) were related to positive PAX5 expression. The MIPI-SP risk scoring system was established and exhibited a superior prognostic value for OS depending on an area under the curve (AUC) of 0.770 (95

Introduction As a member of the protein arginine N-methyltransferase family, protein arginine methyltransferase 1 (PRMT1) plays a crucial regulatory role in the etiology of malignant neoplasms. PRMT1-mediated protein methylation promoted the maintenance of acute myeloid leukemia, which revealed the promising potency of PRMT1 inhibitors. Recent study suggested that dysregulation of PRMT5 promotes Richter's transformation in chronic lymphocytic leukemia (CLL). However, the effects of PRMT1 in the tumorigenesis and progression of CLL still remained ill-defined. Hence, the aim of this study was to investigate the clinical significance and mechanisms of PRMT1 underlying the development of CLL. Methods Peripheral blood samples were collected from 79 newly diagnosed CLL patients (47 males and 32 females; age range 39-85 years, median 63 years) in Shandong Provincial Hospital CLL (SPHCLL) cohort with informed consent. CRISPR-Cas9 technology was used to stably knockout PRMT1 in CLL cells. A label free quantitative proteomics analysis was implemented to reveal the protein methylation mediated by PRMT1. Assessment of cell viability, apoptosis and cell cycle were analyzed by cell counting kit-8, annexin V-PE/7AAD and PI/ RNase staining, respectively. This study was approved by the Medical Ethics Committee of Shandong Provincial Hospital. Results This study examined the expression of PRMT1 in SPHCLL and GEO databases, and discovered the upregulation of PRMT1 mRNA in CLL cells. Aberrantly elevated expression of PRMT1 was observed in a cohort of newly diagnosed CLL patients than healthy donors in mRNA level (donors vs. CLL patients, 0.07±0.06 vs. 0.20 ±0.21, p=0.013). Furthermore, increased expression of PRMT1 was correlated with inferior prognosis in two long-term follow-up cohorts of CLL patients (HR=2.80, p=0.002, and HR=1.551, p=0.009). To elucidate the functional significance of PRMT1 in CLL, we established stable PRMT1 knockdown cells using lentiviral shRNAs and PRMT1 knockout cells using CRISPR/Cas9 technology. The suppression of PRMT1 remarkably inhibited cell proliferation, induced cell apoptosis and blocked cell cycle at G1/S phase in CLL cells. Furthermore, it was observed that C7280948, a selective inhibitor of PRMT1, resulted in the defective proliferation of CLL primary cells in a dose-dependent manner. We subsequently performed pre-clinical investigations of C7280948 in the orthotopic CLL xenograft murine model. Notably, the administration of C7280948 significantly diminished the leukemia burden and induced the lessened degree of splenomegaly in comparison to the control group (Fig. 1A). Moreover, a reduction in the population of CLL cells was detected in bone marrow and spleen of mice treated with C7280948. To decipher the role of PRMT1 in the pathogenesis of CLL, the label free quantitative proteomics analysis was conducted on PRMT1-deficent and control MEC1 cells. Knockdown of PRMT1 diminished asymmetric dimethylarginine of some proteins in CLL cells. In accordance with the results of proteomics analysis, microtubule associated serine/threonine kinase 1 (MAST1) was selected as a candidate target for further investigation. The methylation site of MAST1 protein was identified as R802 (Fig. 1B). Increased expression of MAST1 was correlated with inferior prognosis of CLL patients ( p<0.001), indicating the essential role of MAST1 in the progression of CLL. These results supported the hypothesis that PRMT1 interacted with MAST1 and enhanced the activity of MAST1 via methylating this oncoprotein in CLL cells. Conclusion The present study provides robust evidence for the oncogenic function of PRMT1 in the pathogenesis of CLL, highlighting the potential therapeutic efficacy of the selective PRMT1 inhibitor C7280948. Collectively, the targeted inhibition of PRMT1 exhibits promising prospects for the management of CLL patients.

Introduction: Immune-mediated inflammatory diseases (IMIDs) constitute a clinically heterogeneous group with a disruption of the immune system that provokes inflammation of any organ system on a chronic basis. Previous observational investigations have demonstrated an association between a person's or their family's medical background of IMIDs and a higher likelihood of developing Hodgkin's lymphoma (HL). Nevertheless, the exact causal connection between specific IMIDs and HL remains ambiguous. Therefore, the investigation aims to explore the causal effects between IMIDs and HL. Methods: A two-sample Mendelian randomization (TSMR) approach was employed in this study, using publicly available genome-wide association study summary statistics. The inverse variance weighted (IVW) method was the primary approach used for the Mendelian randomization (MR) analysis. Furthermore, supplementary statistical approaches such as MR-Egger, simple mode, weighted median, and MR-PRESSO were employed. In order to identify potential heterogeneity and pleiotropy, several tests were conducted, including Cochran's Q test, the MR-Egger regression test, and the MR-PRESSO test. Moreover, the leave-one-out method was implemented to examine the reliability of the MR results. Results: Based on the IVW analysis the findings revealed a positive causal link at risk for multiple sclerosis (MS) and HL [odds ratio (OR) = 1.281; 95% CI = 1.087-1.510, p = 0. 003] and a negative causal link at risk for type 1 diabetes (T1D) and HL (OR = 0.853; 95% CI = 0.776-0.937, p = 0.001). However, no significant causal relationship was found between the risk of HL and the other eight IMIDs, including inflammatory bowel diseases (OR = 1.034; 95%CI = 0.910-1.176, p = 0.606), systemic lupus erythematosus (OR = 1.041; 95%CI = 0.944-1.149, p = 0.422), Crohn's disease (OR = 0.952; 95%CI = 1.840-1.078, p = 0.436), ulcerative colitis (OR = 1.042; 95%CI = 0.874-1.242, p = 0.644), primary sclerosing cholangitis (OR = 1.061; 95%CI = 0.937-1.202, p = 0.349), primary biliary cirrhosis (OR = 1.046; 95%CI = 0.918-1.192, p = 0.495), psoriasis (OR = 0.989; 95%CI = 0.954-1.026, p = 0.565), celiac disease (OR = 1.198; 95%CI = 0.911-1.574, p = 0.195). Figure 1 displayed a detailed visual representation of the findings obtained in the study. No indication was made of any potential heterogeneity or horizontal pleiotropy. Besides, no outliers were discovered in the MR using MR-PRESSO. In addition, the leave-one-out analysis indicates that the MR estimates are not driven by any single SNP, suggesting that the observed associations are robust and reliable. Conclusions: The present investigation emphasizes an increased susceptibility of MS to the risk of HL and a potential protective effect of T1D against the risk of HL. In light of these findings, patients with MS receiving immunosuppressive therapy are highly suggested to undergo periodic physical evaluations and lymphoma surveillance. Further investigations are warranted to explore the potential mechanisms of MS and T1D on the development of HL.

Background: Autophagy is a lysosome-mediated catabolic process that maintains cell homeostasis and survival. It occurs not only in normal cells such as cardiac muscle cells, neurons, and pancreatic acinar cells but also in various benign and malignant tumors. The abnormal level of intracellular autophagy is closely related to multiple pathophysiological processes, including aging, neurodegeneration, infectious diseases, immune disorders, and cancer. Autophagy mainly plays a dual role in life and death by regulating cell survival, proliferation, and death, thus being involved in the occurrence, development, and treatment of cancer. It is also involved in chemotherapy resistance by a dual role, since it not only promotes the occurrence of drug resistance but also reverses it. Previous findings suggest that the regulation of autophagy can be used as an effective strategy in tumor therapy. Summary: Recent studies found that small molecules from natural products and their derivatives exert anticancer activity by regulating the level of autophagy in tumor cells. Key Messages: Therefore, this review article describes the mechanism of autophagy, the role of autophagy in normal cells and tumor cells, and the research progress on the anticancer molecular mechanism of targets regulating cell autophagy. The aim is to provide a theoretical basis for developing autophagy inhibitors or activators to improve anticancer efficacy.

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world, with a highly variable clinical course, which makes the study of prognostic influences and treatment options for CLL patients particularly important. Cancer cells readjust their metabolic pathways to accommodate their nutritional demands for reducing equivalents, increased energy and cellular biosynthesis. Altered amino acid metabolism is one way to achieve these demands. Amino acid metabolism plays an important role in the development and progression of CLL. However, there is still a lack of clinical biochemical indicators associated to amino acid metabolism to evaluate the prognosis of CLL patients. Aims: The study aimed to investigate the impact of clinical indicators related to amino acid metabolism on the prognosis of CLL patients and to develop a novel amino acid metabolism scoring system to optimize the risk assessment of CLL patients. Methods: CLL patients who were treated in Shandong Provincial Hospital between October 2010 to April 2022 were assessed from the Shandong Provincial Hospital CLL (SPHCLL) database. The univariate Cox regression analysis and multivariate Cox regression analysis were applied to evaluate the prognostic values of clinical indicators related to amino acid metabolism. Survival curves were constructed using the Kaplan-Meier method. The prognostic capacities of the novel scoring system were measured by areas under the curve (AUCs) of receiver operating characteristic curves. Results: A total of 634 CLL patients were randomly assigned to the training set (n=432) and validation set (n=202). Independent prognostic significance of hemoglobin (Hb, p=0.004), cystatin (Cys, p=0.018) and glutamyl transpeptidase (GGT, p=0.006) was determined in the training set by univariate and multivariate Cox regression analysis. The clinical indicators related to amino acid metabolism, Hb, CysC and GGT, were selected for establishing a novel amino acid metabolism score system (AAMS) model in CLL patients: AAMS= -1.082*Hb+0.862*CysC+0.842*GGT. CLL patients in the training set were divided into low and high subgroups based on the median AAMS. AAMS had independent prognostic significance in the prognosis of CLL patients (p=0.017), and a higher AAMS indicates a poorer prognosis for CLL patients. AAMS (AUC=0.755) also showed better predictive performance compared with Binet stage (AUC=0.568) and Rai stage (AUC=0.592) in CLL patients of the training set. These conclusions are well proved in the validation set. Summary/Conclusion: AAMS was an independent prognostic factor for CLL patients.This study analyzed the prognostic effects of clinical indicators related to amino acid metabolism in patients with CLL and developed a new scoring system to optimize accurate risk assessment in CLL patients. Keywords: Chronic lymphocytic leukemia