Hematology最新文献

Background: Relapsed/Refractory (R/R) diffuse large B-cell lymphoma (DLBCL) represents a subgroup with a high incidence and dismal prognosis. Currently, there is a lack of robust models for predicting R/R DLBCL. Therefore, we conducted a retrospective study to identify key determinants to be incorporated into a novel nomogram to enhance the identification of DLBCL patients at elevated risk of refractoriness/recurrence.

Methods: We included 293 newly-diagnosed DLBCL patients from Harbin Medical University Cancer Hospital, collected from 2008-2017. Patients were randomly divided into a training cohort (n = 206) and a validation cohort (n = 87) at a 7:3 ratio. The training cohort underwent univariable analysis to select variables for a binary logistic regression model. These variables were also prioritized using a random forest algorithm. The developed nomogram was evaluated with the receiver-operator characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) for its clinical utility.

Results: Univariable analysis pinpointed several factors significantly associated with refractoriness/recurrence, including pathological subtype, lactate dehydrogenase (LDH), International Prognostic Index (IPI), treatment, absolute lymphocyte count (ALC), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI). Binary logistic regression highlighted pathological subtype, LDH, treatment, and ALC as key predictors, which were incorporated into the nomogram. The nomogram showed excellent calibration and accuracy in both cohorts, and comparative DCA and ROC analysis demonstrated its superior net benefit and area under the curve (AUC) compared to traditional indexes like IPI, R-IPI, and NCCN-IPI.

Conclusion: This nomogram serves as a valuable tool for predicting the likelihood of refractoriness or recurrence in DLBCL patients.

Objective: Liquid-liquid phase separation (LLPS) may affect the therapeutic sensitivity of multiple myeloma (MM). This study aimed to identify LLPS-related genes with MM prognostic values and to confirm their effects on tumor progression.

Methods: Based on public transcriptomic data, this study screened LLPS- and immune-related genes for MM-derived plasma cells. Subtypes were identified using consensus clustering, followed by comparisons using t-test and survival analysis. Least absolute shrinkage and selection operator was implemented to screen prognostic signatures, and Kaplan-Meier and receiver operator characteristic curves were plotted to assess their prognostic values. After transfected with sh-DDX21, CCK8, flow cytometry, and Transwells were used to observe MM cell proliferation, apoptosis, migration, and invasion.

Results: By overlapping LLPS- and immune-related genes, 103 genes were obtained to cluster MM samples into three subtypes, which had significant differences in survival and immune landscape. Cox regression analysis screened out EZH2 and DDX21 that significantly overexpressed in MM to construct a prognostic model, with superior performance in predicting MM prognostic risks. Notably, subtype2 with more adverse prognosis showed significantly elevated risk scores and was more distributed in groups with high prognostic risk. In vitro experiments confirmed that cell proliferation, invasion, and migration were significantly inhibited in MM.1S cells transfected with sh-DDX21.

Conclusion: LLPS-related EZH2 and DDX21 were novel markers to predict prognostic risk of MM. Among them, DDX21 was experimentally confirmed to promote MM cell proliferation, migration and invasion. These potential prognostic markers could be targeted in future personalized therapeutic strategies for MM, potentially improving patient outcomes.

Objectives: Currently, there is limited understanding regarding the prognostic significance of time to progression (TTP) after first remission in multiple myeloma (MM).

Methods: We conducted a retrospective analysis of clinical data from 209 patients with MM. These patients were categorized into ≤ 6 months, ≤ 12 months, ≤ 24 months, > 24 months, 6-12 months, and 12-24 months subgroups based on TTP.

Results: Patients in ≤ 12 months group exhibited shorter median overall survival (OS) and OS-1 compared to those in ≤ 24 months group (61.73 vs 96.10 months, P = 0.02; 54.00 vs 74.17 months, P = 0.048). ≤ 6 months group exhibited shorter median OS and OS-1 compared to 6-12 months group (33.63 vs 79.60 months, P = 0.022; 19.93 vs 65.17 months, P = 0.015). Patients in 6-12 months group had shorter median OS and OS-1 compared to those in 12-24 months group (79.60 vs 100.43 months, P < 0.001; 65.17 vs 77.17 months, P = 0.012).No significant difference in OS was observed between patients in 12-24 months and > 24 months groups. For patients who experienced progression within 12 or 24 months after remission, undergoing autologous hematopoietic stem cell transplantation (ASCT) after progression conferred a median OS and OS-2 advantage over receiving post-progression chemotherapy. Multivariable analysis confirmed that TTP was an independent predictor for OS in patients with MM.

Conclusion: Patients with MM who experience earlier disease progression within 12 months after remission have a worse prognosis, and post-progression ASCT can improve their survival outcomes.

Objective: Acute myeloid leukemia (AML) exhibits significant heterogeneity and aggressiveness. This study aimed to investigate T cell heterogeneity in the AML tumor microenvironment using single-cell RNA sequencing (scRNA-seq) and identify potential biomarkers for prognosis and precision therapy.

Methods: scRNA-seq data from AML patient samples were analyzed to identify T cell subsets. A prognostic risk model was constructed using random forest and LASSO regression analyses based on key genes derived from a specific T cell cluster (Cluster 4). The model's predictive performance was validated using external datasets.

Results: Analysis revealed significant functional heterogeneity among T cell subsets. Cluster 4 T cells showed distinct gene set activities related to immune regulation. Three genes - BSG, PPARD, and SLC16A8 - were identified as independent prognostic factors. The risk model effectively stratified patients into high-risk and low-risk groups, with the high-risk group demonstrating significantly poorer survival outcomes. The model showed robust predictive accuracy, with areas under the ROC curve of 0.78, 0.86, and 0.86 for 1-, 3-, and 5-year survival, respectively.

Conclusion: This study highlights the functional diversity of T cells in AML and identifies BSG, PPARD, and SLC16A8 as promising biomarkers for prognostic stratification. The developed risk model provides a valuable tool for guiding personalized treatment strategies in AML.

Background: Luspatercept, approved by the FDA and EMA for patients with transfusion-dependent lower-risk myelodysplastic syndrome (LR-MDS) unresponsive to erythropoiesis-stimulating agents (ESAs), lacks extensive real-world data, particularly in China.

Methods: We retrospectively analyzed 14 LR-MDS-SF3B1 patients treated with luspatercept for ≥12 weeks.

Results: Median age was 60 years (range 47-72); 42.9% were male. Before treatment, 78.6% were transfusion-dependent, and 42.9% had prior ESA therapy. At median 24-week follow-up (range 12-44), erythroid response rates were 71.43% (week 12), 75.00% (week 16), and 62.50% (week 24). Hemoglobin levels significantly improved at weeks 12 and 24 (P = 0.013, P = 0.005). No grade 3-4 adverse events occurred. Hematologic improvement-erythroid (HI-E) patients exhibited higher white blood cells, neutrophils, and reticulocytes at week 12 versus non-HI-E patients. Bone marrow analysis revealed erythroid hyperplasia in HI-E patients, with higher erythrocyte percentage (56.00% vs. 34.00%, P = 0.023), lower myeloid-to-erythroid ratio (0.60 vs. 1.59, P = 0.024), and increased polychromatic erythroblasts (19.50% vs. 10.00%, P = 0.034).

Conclusions: Luspatercept demonstrated efficacy and safety in Chinese LR-MDSSF3B1 patients. Greater erythroid hyperplasia correlated with better clinical response.

Objectives: Acquired aplastic anemia (AA) is a bone marrow failure syndrome whose pathogenesis remains incompletely understood. This study aimed to explore the genetic determinants underlying AA and identify potential therapeutic targets.

Methods: We integrated summary data - based Mendelian randomization (SMR) and colocalization analysis to identify genes causally linked to AA. Key candidates were validated using single-cell RNA sequencing to assess their expression and pseudotime dynamics. We explored B-cell - mediated cell communication related to immunosuppressive therapy response. Serum expression of candidate genes was validated and correlated with clinical outcomes.

Results: SMR analysis identified 28 genes significantly associated with AA, among which NFKB1 emerged as a central regulatory factor. scRNA-seq data confirmed NFKB1's differential expression in B cells and its dynamic regulation during disease progression. Discussion and conclusion: This study is the first to comprehensively characterize the role of NFKB1 in the pathogenesis of AA through integrated multi-omics analysis and providing novel insights for the development of targeted interventions.

Objectives: To explore the differences between primary immune thrombocytopenia (ITP) and ITP secondary to connective tissue disease (CTD-ITP).

Methods: A retrospective observational study was conducted on patients newly diagnosed with primary ITP and CTD-ITP hospitalized in the Hematology Department of Tianjin Medical University General Hospital from July 1, 2019 to December 31, 2023. Data, including demographic details, medical history records, and laboratory test results, were collected, followed by a comparative analysis to identify differences between the groups.

Results: Compared with patients in the primary ITP group, those in the CTD-ITP group exhibited a female predominance, along with lower platelet and hemoglobin levels. Total globulin and immunoglobulin G (IgG) concentrations were higher in the CTD-ITP group than in the primary ITP group, whereas albumin, complement C3, and C4 levels were lower. Antinuclear antibody titers were higher in the CTD-ITP group, and the percentages of regulatory B (Breg) cells and transitional B cells were lower. A greater percentage of abnormal megakaryocytes was observed in the CTD-ITP group. Furthermore, a larger proportion of patients in the CTD-ITP group met treatment criteria, necessitated more intensive therapy, and required a longer duration to achieve complete remission.

Conclusion: Compared with patients in the primary ITP group, those in the CTD-ITP group had more severe conditions, more intense immune disturbances, and greater treatment challenges. Individualized treatment is needed.

Objective: Venous thromboembolism (VTE) is a significant global health concern. Recent investigations indicate that anemia may increase the risk of VTE. Nevertheless, the presence of confounding variables in observational studies has rendered the causal association between anemia and VTE inconclusive.

Methods: This study utilized a two-sample Mendelian Randomization methodology, employing genetic variants derived from specific large-scale genome-wide association studies as instrumental variables to investigate the causal relationship between anemia and VTE. Rigorous statistical analyses were conducted, including the primary analysis based on the inverse-variance weighted (IVW) method, along with supplementary analyses such as MR-Egger, weighted median, and MR-PRESSO, to ensure the reliability and validity of our results.

Results: Our analysis suggests a potential causal association between anemia and certain thrombotic events. Anemia was associated with an increased risk of thrombosis and embolism in unusual sites (OR = 1.446, 95% CI: 1.104-1.895, p = 0.007), while aplastic anemia showed a weak positive association with overall VTE risk (OR = 1.065, 95% CI: 1.003-1.131, p = 0.040).

Conclusions: Anemia individuals face an increased risk of embolism and thrombosis events, and AA exhibits a potential association with VTE. Nevertheless, a comprehensive comprehension of the precise underlying mechanisms linking anemia/AA and VTE necessitates further exploration through supplementary research.

To investigate the role of ALKBH3 in acute myeloid leukemia (AML), we constructed an animal model of xenotransplantation of AML. Our study demonstrated that ALKBH3-mediated m1A demethylation inhibits ferroptosis in KG-1 cells by increasing ATF4 expression, thus promoting the development of AML. These findings suggest that reducing ALKBH3 expression may be a potential strategy to mitigate AML progression.

Background: Acute myeloid leukemia (AML) is characterized by the unrestrained proliferation of myeloid cells. Studies have shown that ALKBH3 is upregulated in most tumors, but the role of ALKBH3 in AML remains unclear.Methods: In this study, we investigated the function of ALKBH3 in AML cells (KG-1) by immunofluorescence, ELISA, flow cytometry, HE staining, and Western blotting.Results: Our results revealed that ALKBH3 is upregulated in AML and that the downregulation of ALKBH3 inhibited KG-1 cell proliferation and promoted cell apoptosis; at the same time, ALKBH3 upregulated ATF4 expression through m1A demethylation, and the knockdown of ATF4 resulted in increased ferrous iron content; TFR1, ACSL4, and PTGS2 expression; and ROS and MDA levels, whereas SOD and GSH levels and the expression levels of ATF4, SLC7A11, GPX4, and FTH1 decreased in KG-1 cells, thereby promoting ferroptosis. Mechanistically, ALKBH3-mediated m1A demethylation suppressed ferroptosis in KG-1 cells by increasing ATF4 expression, thereby promoting the development of AML.Conclusions: Our study indicated that reducing the expression of ALKBH3 might be a potential target for improving AML symptoms.

Introduction: Cases of warm autoimmune hemolytic anemia (wAIHA) often present with life-threatening levels of hemoglobin requiring red blood cell (RBC) transfusion support.

Aim: This literature review assessed the occurrence, safety, effectiveness, and hospitalization burden of RBC transfusions in the management of patients with wAIHA.

Methods: Electronic databases (Embase, MEDLINE) were searched from inception to December 2021 along with additional searches conducted up to March 2024.

Results: Of the 1478 articles screened, 17 observational studies and reviews were included. These studies demonstrated the use of 1-50 red blood cell transfusions to reach clinically acceptable hemoglobin levels in patients with wAIHA. In general, pre-transfusion hemoglobin levels were 6 g/dL and increased by an average 1.2 g/dL following a transfusion. Approximately 50% of patients with primary or secondary wAIHA suffered relapses. No data was available to distinguish between RBC transfusions used at initial presentation versus during relapse. Five studies found no increase in hemolysis or serious adverse reactions following transfusions and two studies reported mild transfusion-related adverse effects. Limited data was available regarding the hospitalization burden of RBC transfusion. Patients with wAIHA requiring transfusions had a median hospital stay from 15 to 17 days, which is considerably higher than all causes hospitalization of 4.5 days for 2023 U.S.

Conclusion: In patients with wAIHA, data supports wide variability in occurrence, but relative safety and effectiveness of RBC transfusions as supportive therapy. Additional studies are needed to assess the occurrence, safety, and hospitalization burden of RBC transfusions relative to other therapies in chronic relapsing wAIHA.