Hematology最新文献

Objective: This study aimed to identify neutrophil extracellular trap-related genes (NET-RGs), explore their prognostic significance, and predict drug interactions in peripheral T-cell lymphoma (PTCL).

Methods: Differentially expressed NET-RGs (DE-NRGs) between PTCL and normal tissues were screened. Functional enrichment analysis was conducted. Bioinformatics and machine learning were used to identify hub genes and assess their diagnostic value. Univariate and multivariate analyses were used to evaluate prognostic roles. Correlation and immune infiltration analyses were performed to explore relationships with the tumor microenvironment (TME). Clinical data were collected from PTCL patients who received potential agents (lenalidomide) as first-line treatment.

Results: A total of 31 DE-NRGs were identified (18 upregulated and 13 downregulated), enriched in inflammatory response, extracellular matrix organization, and infection involvement. Four hub genes (AKT2, MAPK14, IRF1, and TNF) were identified as effective PTCL diagnostic markers. Higher AKT2/MAPK14 expression correlated with poorer overall survival (OS), while elevated TNF expression associated with better OS; AKT2 and TNF independently predicted OS. These genes were implicated in modulating TME remodeling. Potential therapeutic agents (e.g. capivasertib, lenalidomide) were predicted, and lenalidomide may represent a feasible initial treatment option for PTCL, with an objective response rate (ORR) of 40.0% and a maximum survival duration exceeding 50 months.

Conclusion: NET-RGs play crucial roles in diagnosis, prognosis, and TME regulation, and lenalidomide, a putative TNF-targeting agent, may represent a feasible initial treatment option in PTCL.

Objectives: Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are closely related hematologic malignancies. However, the transcriptomic distinctions between them are not fully elucidated. This study aimed to identify transcriptional differences between MDS and AML using whole transcriptome sequencing to provide a theoretical basis for improved diagnosis and treatment.

Methods: Whole transcriptome sequencing was conducted to profile the expression of mRNAs and non-coding RNAs in MDS and AML samples. Subsequent bioinformatic analyzes were performed to identify differentially expressed genes and their potential functional roles.

Results: Comprehensive sequencing revealed 1926 differentially expressed mRNAs, 80 miRNAs, 1553 lncRNAs, and 1635 circRNAs between MDS and AML. Functional enrichment analysis indicated that these differentially expressed genes are predominantly involved in key pathways such as ferroptosis, immune response, and cell cycle regulation. Further investigation highlighted a significant association of differentially expressed lncRNAs and circRNAs with the ferroptosis pathway. Key molecules implicated in ferroptosis included AQP3, ALOX5, ADAM23, STK11, AIFM2, hsa-miR-4433b-3p, hsa-miR-1307-3p, hsa-miR-23a-5p, and hsa-miR-3916.

Discussion: The distinct transcriptomic profiles uncovered in this study reveal critical molecular differences in the pathogenesis of MDS and AML. The strong enrichment of ferroptosis-related pathways, mediated by specific coding and non-coding RNAs, suggests a pivotal role for this biological process in disease development and progression from MDS to AML.

Conclusion: Our study identified crucial genes and non-coding RNAs linked to ferroptosis, implicating their potential roles in MDS and AML pathogenesis and offering valuable candidate targets for future research.

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.

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.

Background: Relapsed immune thrombocytopenia (ITP) poses challenges in treatment. Thrombopoietin receptor agonists (TPO-RAs) are recommended as second-line therapy, but the efficacy of monotherapy is limited to about 60%. Our preliminary studies suggest sirolimus is effective for relapsed ITP. This study aimed to evaluate the efficacy and safety of TPO-RA combined with sirolimus in treating relapsed ITP.

Methods: A retrospective analysis was conducted on 50 patients with relapsed ITP, all of whom received TPO-RAs (hetrombopag and eltrombopag) combined with sirolimus therapy. The primary endpoints were the overall response rate (ORR) at 4, 8, and 12 weeks of treatment. Secondary endpoints included safety of this regimen and subgroup analysis.

Results: ORR at 4, 8, and 12 weeks was 61%, 76%, and 82%, respectively, with a median time to response of 7 days. Mean platelet counts at 2-, 4-, 8-, and 12-weeks post-treatment were 71 ± 12.7 × 10⁹/L, 86 ± 10.9 × 10⁹/L, 128 ± 19.7 × 10⁹/L and 131 ± 17.2 × 10⁹/L, respectively. Whether it is hetrombopag or eltrombopag, when combined with sirolimus, there is no statistically significant difference in efficacy between the two subgroups. TPORAs combined with sirolimus as second-line treatment and as third-line or beyond treatment showed no difference in efficacy. Among ANA-positive patients, the ORR shows no significant difference compared to the ANA-negative group (p > 0.05). Patients with ITP for less than one year are more likely to benefit from this treatment regimen (p = 0.003).

Conclusions: The combination of TPO-RAs and sirolimus significantly improved platelet counts and sustained response rates. The regimen demonstrated a manageable safety profile, offering a novel therapeutic option for relapsed ITP.

Background and objectives: Blood transfusion is a vital medical procedure, yet it carries the risk of transmitting infectious diseases. This study aimed to assess the demographic characteristics and transfusion-transmitted infection (TTI) profiles of family replacement and voluntary blood donors in Saudi Arabia.

Materials and methods: A retrospective cross-sectional analysis was conducted using records from 49,590 blood donors at King Fahad Medical City, Riyadh, Saudi Arabia. Donors were classified as family replacement or voluntary. Demographic information and results of screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), syphilis, and malaria were analysed. Statistical analyses included descriptive statistics, chi-square testing, stratified analysis by nationality, and logistic regression.

Results: 49,590 donors were included, 10.6% were family replacement and 89.4% were voluntary. Males accounted for 92.6% of the donor population. No significant differences were observed between the two groups for HBV, HCV, HIV, or syphilis. However, malaria prevalence was significantly higher among family replacement donors (5.3%) compared to voluntary donors (2.9%). Family replacement donation was more common among younger donors, males, and non-Saudi nationals.‏ The higher malaria prevalence among family replacement donors was particularly evident among non-Saudi donors, and regression analysis confirmed that nationality modified the association between donation type and malaria positivity.

Conclusion: While rates of major viral TTIs were comparable between donor types, malaria risk was significantly higher among family replacement donors, especially among non-Saudi donors. These findings highlight the importance of continued malaria screening and donor selection strategies to maintain safe blood transfusion practices in Saudi Arabia.

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.