Hematology最新文献

Objectives: To elucidate the mechanisms by which leukemia-derived exosomes induce immunosuppression in dendritic cells (DCs) and identify potential therapeutic targets.

Methods: The optimal exosome dosage (20 µg/ml) for DC treatment was determined via gradient concentration experiments. Transcriptomics and qPCR validation explored molecular pathways. DC phenotype was assessed for maturation markers (CD83/CD86), antigen presentation (CD1a), and immune receptors (TLR2). Cytokine levels (IL-6, IL-17, TNF-α, IL-4) were quantified. Multi-omics analysis identified key signaling pathways. Clinical validation utilized samples from AML patients.

Results: Exosome treatment induced broad DC immunosuppression, characterized by significant downregulation of pro-inflammatory cytokines (IL-6, IL-17, TNF-α) and upregulation of anti-inflammatory IL-4. Phenotypic analysis revealed selective inhibition of CD1a and TLR2, while maturation markers (CD83/CD86) remained unaltered. Multi-omics identified TNF-β signaling as the primary immunosuppressive pathway. qPCR confirmed elevated TGF-β2 and mitochondrial ribosomal protein MRPL58, alongside reduced TLR2. Clinical studies in AML patients validated upregulation of TGF-β2, MRPL58, and exosomal markers. Exosomes impaired DC antigen presentation, immune response, and metabolic activity.

Discussion: MRPL58 is a novel mediator of exosome-driven immunosuppression, implicating metabolic reprograming. Selective CD1a/TLR2 inhibition suggests exosomes evade immune detection while permitting DC maturation, a strategy favoring leukemia immune escape. Targeting exosome-DC interactions (e.g. blocking exosomal signals or MRPL58) may restore anti-tumor immunity.

Conclusion: Leukemia exosomes suppress DC function primarily through MRPL58-associated metabolic modulation and TNF-β signaling. MRPL58 represents a promising therapeutic target. Disrupting exosome-mediated immunosuppression could enhance DC-based vaccines and combination immunotherapies for leukemia.

Purpose: This study aims to determine the proportion of bone marrow dysplasia in advance of HIV infection.

Patients and methods: A cross-sectional study was conducted on advanced HIV patients, stage III and IV, with cytopenia at Hasan Sadikin General Hospital, Bandung, from January 2021 to November 2023. Patient characteristics and laboratory data were obtained from patients diagnosed with HIV stages III and IV who presented with cytopenia and underwent bone marrow examinations, as documented in the medical records. The differences between the two groups were analyzed using the Mann-Whitney U test or the Independent T-test for numerical data and Chi-square or Fisher's exact for categorical data.

Results: A total of 42 subjects were enrolled, consisting of 8 (19%) HIV stage III and 34 (81%) stage IV patients. Patients with HIV stage IV exhibited a higher incidence of pancytopenia, with 15 cases (44.1%). The bone marrow cellularity in HIV stage IV was predominantly hypocellular, accounting for 22 cases (64.7%). Dyserythropoiesis was the most common type of bone marrow dysplasia observed in HIV stage IV, present in 19 cases (55.9%). The prevalence of Bone Marrow Dysplasia in HIV stage IV was higher than in HIV stage III, with 23 (64.7%) and 2 (37.5%), respectively (p = 0.2348).

Conclusion: Cytopenias related to HIV are common and tend to worsen as the disease advances. This emphasizes the importance of investigating the potential for bone marrow dysplasia and conducting cytogenetic diagnostic testing for myelodysplastic syndromes (MDS), as a significant non-AIDS-defining hematological malignancy in individuals with advanced HIV.

Background: Congenital thrombocytopenia represents a diagnostically challenging group of disorders due to overlapping clinical presentations among various etiologies.

Case presentation: A 3-month-old infant presented with severe thrombocytopenia (platelet count 6,000/μL), neutropenia, and bone marrow findings of megakaryocytic hypoplasia, initially suggestive of congenital amegakaryocytic thrombocytopenia (CAMT). Comprehensive genetic testing identified a homozygous pathogenic variant in the GNE gene (NM_001128227.2:c.1768G > A, p.Gly590Arg), establishing the definitive diagnosis of GNE-related thrombocytopenia (Thrombocytopenia-12, THC12).

Clinical significance: This case highlights three critical aspects: first, the essential role of genetic testing in differentiating congenital thrombocytopenias; second, the distinct management implications of THC12 compared to CAMT; and third, the need for long-term monitoring given the potential for late-onset myopathy despite initial isolated hematologic manifestations.

Management: Therapeutic interventions included intravenous immunoglobulin, platelet transfusions, and thrombopoietin receptor agonists, with concurrent evaluation for potential hematopoietic stem cell transplantation.

Conclusion: This report underscores THC12 as an important diagnostic consideration in infants with congenital thrombocytopenia and emphasizes the necessity of genetic confirmation to guide appropriate clinical management and family counseling.

Objectives: Dysregulation of apoptosis-related genes (ARGs) may contribute to tumorigenesis and impact patient prognosis, but their specific influence on prognosis and immune characteristics in diffuse large B-cell lymphoma (DLBCL) remains unclear.

Methods: Gene expression profiles were collected from GEO datasets GSE10846 (training set; n = 414) and GSE181063 (validation set; n = 1310), totaling 1724 DLBCL samples. Univariate Cox and LASSO Cox regression analyses were performed to identified key ARGs, which were used to construct a risk score model. Patients were stratified into high/low-risk groups using the risk score. Functional enrichment analyses were conducted to explore biological functions and pathways. Immune cell infiltration was assessed using the CIBERSORT algorithm.

Results: 39 ARGs were significantly associated with overall survival in DLBCL patients. The risk score model effectively stratified patients into high/low-risk groups with distinct survival outcomes. Consensus clustering revealed distinct molecular subtypes with varying prognoses and biological characteristics. Enrichment analyses indicated that the prognostic genes are involved in critical pathways related to apoptosis and immune responses. High-risk patients exhibited higher immune scores and a distinct tumor immune microenvironment.

Conclusion: Apoptosis-related genes are valuable prognostic biomarkers in DLBCL and are associated with distinct immune characteristics. The risk model may aid in personalized risk assessment and inform treatment strategies. These findings provide insights into potential therapeutic targets by modulating apoptosis and immune responses in DLBCL.

Objectives: The 4.2-kb deletion (-α^4.2) is a common cause of α-thalassemia in southern China. However, the molecular characteristics and clinical phenotypes of its subtypes remain incompletely characterized. This study aims to investigate these knowledge gaps for -α^4.2 subtypes, explore their formation mechanisms, and determine their association with HBA1:c.223G>C (p.Asp75His; Hb Q-Thailand).

Methods: We retrospectively analyzed α-thalassemia testing data from 18,050 individuals, identifying 112 -α^4.2 carriers previously characterized by Multiplex Ligation-dependent Probe Amplification (MLPA). Those MLPA data were used for subtyping. Sanger sequencing detected HBA1:c.223G>C and deletion breakpoints. Bioinformatics analyzed subtype distinctions. Associated hematological parameters were evaluated for clinical significance.

Results: MLPA subtyped 98.2% (110/112) carriers: 88.2% (97/110) as -α^4.2 (C) and 11.8% (13/110) as -α^4.2 (B). HBA1:c.223G>C displayed strong linkage with -α^4.2 (B) [11/13 cases; termed -α^4.2-Q (B)], but not with -α^4.2 (C). Notably, we recognized two novel -α^4.2 (B) cases lacking this mutation [-α^{4.2-without Q association} (B)], representing the first report of such variants. Breakpoint analyses showed distinct structural features: -α^4.2 (C) has an A-rich sequence with single-stranded characteristics, while -α^4.2 (B) predictedly forms complex stable secondary structures. Hematological analysis showed that -α^4.2-Q (B) exhibited the characteristic Hb Q-Thailand pattern, while -α^{4.2-without Q association} (B) had parameters similar to -α^4.2 (C).

Conclusion: Based on this systematic analysis, we proposed a dual-mechanism hypothesis ('functional trigger + linkage maintenance') to explain the Hb Q-Thailand/-α^4.2 (B) association. Hematological findings were consistent. These results deepen our understanding of the molecular and clinical characteristics of -α^4.2 subtypes, helping clinicians provide more precise counseling.

Objectives: Evaluate the gamma-glutamyl transpeptidase-to-albumin ratio (GAR) as a prognostic biomarker in acute myeloid leukemia (AML).

Methods: We retrospectively analyzed the data of 162 patients with AML. Receiver operating characteristic (ROC) curve analysis determined the optimal cutoff value for GAR. Multivariate analysis was performed to assess the independent prognostic role of GAR for overall survival (OS) and event-free survival (EFS). Subgroup analysis was conducted to explore the impact of GAR in specific patient groups.

Results: ROC curve analysis showed an optimal cutoff value of 0.84 for GAR. Multivariate analysis revealed that GAR was an independent prognostic factor for OS and EFS. Subgroup analysis demonstrated that a high GAR was associated with shorter OS and EFS in patients with intermediate-risk stratification, those aged ≥60 years, or those that have not undergone hematopoietic stem cell transplantation.

Discussion: GAR reflects nutrition, inflammation, and oxidative stress. This study shows its potential to supplement existing AML risk stratification. Future prospective studies are needed to validate its clinical utility.

Conclusion: We propose GAR as a prognostic biomarker in AML cases, providing a new perspective for prognostic assessment.

Objectives: To investigate to investigate the role of circ_0000075 levels and its regulatory mechanism in patients with acute myeloid leukemia (AML).

Methods: A total of 115 patients with AML and 60 patients with non-haematological tumors (control group) were included. Bone marrow fluid was collected, and the patients were followed-up for a 5-year postoperative prognosis. RT-qPCR was used to detect the expression of circ_0000075 and miR-218-5p, Kaplan-Meier curves recorded for prognostic survival, and multivariate Cox regression analysis to assess factors affecting patient mortality. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8), and Transwell assays were performed to study cell migration and invasion. A dual-luciferase reporter assay verified the interaction between the interaction between circ_0000075 and miR-218-5p.

Results: High levels of circ_0000075 were present in AML patients and correlated with their pathological features. AML patients with high circ_0000075 expression had lower survival rates, and circ_0000075 was predicted to be a risk factor for poor prognosis in AML patients. circ_0000075 levels were elevated in AML cells compared to normal cells, and silencing circ_0000075 attenuated cancer cell proliferation, migration, and invasion. miR-218-5p has abundant circ_0000075 binding sites, and its expression is markedly suppressed in cancer tissues. A dual-luciferase reporter assay demonstrated a targeting relationship between circ_0000075 and miR-218-5p. Response experiments suggested that the use of miRNA inhibitors promoted AML cell function.

Conclusion: circ_0000075 is a risk factor for poor prognosis in AML patients. Silenced circ_0000075 blocks the function of tumor cells mainly by promoting miR-218-5p expression.

The impact of epigenetic modifier gene mutations (EMMs) on the prognosis of patients with acute lymphoblastic leukemia (ALL) is controversial, which is unlike AML. A meta-analysis is needed to evaluate the prognostic value of EMMs in ALL.

Three databases, including PubMed, EMBase and Web of Science, were retrieved to find out studies exploring the association of EMMs and survival outcomes in ALL. Pooled hazard ratios (HRs) and 95% confidential interval (95%CI) were used to assess the impact of EMMs.

Nineteen studies were included in our meta-analysis. DNMT3A mutation was an adverse prognostic factor in overall survival (OS) in patients with ALL (HR, 4.143; P < 0.001) as well as adult T-ALL patients (HR, 3.746; P < 0.001) and those with early T-ALL (HR, 3.523; P = 0.001). IDH mutation also had an unfavorable impact on OS in ALL (HR, 3.583; P < 0.001) and adult T-ALL cohort (HR, 3.562; P < 0.001). For pediatric patients, mutant PHF6 was significantly associated with worse OS in both B-ALL (HR, 3.194; P = 0.026) and T-ALL (HR, 2.125; P = 0.033), while PHF6 mutation had no prognostic impact on the survival of adult T-ALL patients. In addition, patients with KMT2A mutation had shorter OS compared to those with wild type (HR, 4.605; P = 0.045), whereas other EMMs had no impact on prognosis in any type of ALL.

Mutations in DNMT3A, IDH, PHF6 and KMT2A showed a significant prognostic effect in ALL or in its specific subtypes, which might contribute to risk stratification and treatment guidance in the management of ALL patients.

Objectives: The introduction of novel therapies has markedly improved the prognosis of multiple myeloma (MM), yet relapse remains common. For patients with relapsed or refractory multiple myeloma (RRMM), immunotherapy - particularly chimeric antigen receptor T-cell (CAR-T) therapy - shows significant promise. This review summarizes current evidence on CAR-T efficacy and safety.Methods: We performed a systematic review of studies published between 1 January 2021 and 1 August 2024 in PubMed, Web of Science, and Embase. Of 4,301 articles identified, 29 met inclusion criteria.Results: Our findings demonstrate that CAR-T therapy is highly effective in the treatment of RRMM, with an overall response rate (ORR) of 86%. Among responders, the minimal residual disease (MRD) negativity rate was 78%. The median progression-free survival (mPFS) was 9.88 months, and the median duration of response (mDOR) was 12.17 months. In terms of safety, cytokine release syndrome (CRS) occurred in 83% of patients (any grade), with 5% experiencing grade ≥3 CRS. The incidence of grade ≥3 neurotoxicity (NT) was 2%. Infections were reported in 50% of patients (any grade), with 21% experiencing grade ≥3 infections.Conclusion: This meta-analysis provides robust evidence supporting the clinical application of CAR-T therapy in the management of relapsed or refractory multiple myeloma.

Background: Thrombotic diseases are a global challenge. Warfarin remains the anticoagulant of choice in low- and middle-income countries. In 2017, a study reported suboptimal anticoagulation control of 29.4%, compared to the target of ≥ 65%, in patients who attended the Windhoek Central Hospital's warfarin clinic. Objective: Factors contributing to the suboptimal anticoagulation control had to be explored. Methods: To achieve this, 72 patients from the interventional cohort at the clinic were interviewed. Results: The majority (39%) of respondents had dosage-related factors, followed by 21% with diet-related factors, 19% reported factors associated with social determinants of health, and the least (5.6%) due to drug interactions in patients with a co-diagnosis of tuberculosis. Conclusion: The study highlighted the need for improved healthcare system support, such as equipping non-physician health cadres (pharmacists and nurses) with the ability to prescribe warfarin therapy and roll out point-of-care testing for patients with limited access to primary healthcare settings, improving access to medication at the primary healthcare facilities, and patient education to improve warfarin therapy outcomes.