OBJECTIVE:This study aimed to develop a mitochondrial and hematopoiesis-related differentially expressed genes (MH-related DEGs) signature for Myelodysplastic syndromes (MDS) diagnosis and to characterize its regulatory network and immune microenvironment. METHODS:MH-related DEGs were defined as the intersection of differentially expressed genes from three integrated microarray datasets (GSE145733, GSE19429, GSE81173) with a curated set of mitochondrial- and hematopoiesis-related genes from public databases. Functional enrichment, machine learning (logistic regression, support vector machine, LASSO), regulatory network (transcription factors, miRNA, RNA-binding proteins, and drug targets), immune infiltration characterization (ssGSEA), and RT-qPCR assessment were performed. RESULTS:Twenty-nine MH-related DEGs were identified, significantly enriched in MAPK and PI3K-Akt pathways. A 17-gene diagnostic signature showed high accuracy for MDS detection (AUC = 0.963). FGF2 was the highest-weighted predictor, with upregulation supported by RT-qPCR (p < 0.05), and potentially regulated by RUNX1 and miR-15/16/195/424/497 family. Valproic acid was predicted to be associated with multiple signature genes. Two MDS clusters with distinct immune infiltration patterns were identified, where CREB1 correlated with effector memory CD4 T cells in Cluster 1 (r = 0.461), while KITLG correlated with T follicular helper cells in Cluster 2 (r = 0.546), potentially co-regulated by the miR-27. DISCUSSION:This study proposes a mitochondrial-hematopoietic regulatory axis in MDS, with FGF2 as a candidate hub. The clusters and valproic acid prediction offer insights into advancing personalized diagnostics and combination therapy in MDS. CONCLUSION:We developed a candidate signature requiring further validation and uncovered regulatory interactions linking mitochondrial dysfunction to immune dysregulation in MDS.
INTRODUCTION:Assessment of measurable residual disease (MRD) in multiple myeloma (MM) often relies on repeated bone marrow evaluations, which are invasive, costly, and not universally accessible. Alternative monitoring approaches based on routinely available laboratory tests may provide clinically relevant prognostic information. OBJECTIVES:To evaluate whether longitudinal follow-up based exclusively on serologic monitoring can predict survival outcomes in a real-world cohort of patients with MM. METHODS:This retrospective single-center study included 88 consecutive patients diagnosed with MM between 1999 and 2024. All patients underwent bone marrow evaluation at diagnosis and were subsequently monitored using serial serum protein electrophoresis (SPEP) and immunofixation (IF), with serum free light chain (sFLC) assays when available. Serologic undetectability was defined as negative SPEP/IF together with normalization of the κ/λ sFLC ratio. Patients with missing sFLC assays were conservatively analyzed in the serologically positive cohort. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier methods, log-rank testing, and univariable Cox proportional hazards models, taking into account potential guarantee-time (immortal-time) bias associated with post-baseline response endpoints. RESULTS:Overall, 52 patients (59.1%) achieved disappearance of the monoclonal band on SPEP/IF. Twenty-nine patients (33.0%) met all criteria for complete serologic undetectability. Achievement of serologic undetectability was associated with a significantly lower risk of death (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.19-0.91; p=0.0483) and significantly longer PFS (HR 0.195, 95% CI 0.091-0.418; p=0.0028). Disease progression or relapse occurred in 28 patients overall. Among patients who achieved serologic undetectability, those undergoing autologous stem cell transplantation (ASCT) showed a numerical trend toward improved outcomes; however, differences did not reach statistical significance due to sample size constraints. DISCUSSION:These findings suggest that sustained serologic clearance of monoclonal protein reflects deeper disease control and may serve as a clinically meaningful prognostic marker of treatment response. In resource-limited settings or centers where serial bone marrow-based MRD assessment is impractical, comprehensive serologic monitoring offers a feasible, non-invasive alternative for longitudinal disease evaluation. CONCLUSION:In routine clinical practice, achievement of serologic undetectability defined by standard laboratory assays was associated with superior OS and PFS. These results support the prognostic value of accessible serologic monitoring strategies when repeated bone marrow-based MRD evaluations are not feasible.
OBJECTIVES:To investigate the clinical laboratory characteristics and gene mutation features of dual-driver gene positivity in patients with Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-negative MPN). METHODS:We conducted a retrospective analysis of clinical data and genetic test results from 203 newly diagnosed patients with Ph-negative MPN. Of these, 194 had single-driver gene positivity and 9 had dual-driver gene positivity. High-throughput sequencing was used to detect mutations in JAK2, CALR, and MPL. Clinical characteristics and gene mutation profiles were compared between the two patient groups. RESULTS:The incidence of dual-driver gene positivity was 4.4% (9/203), with the most common combinations being JAK2 with CALR (4 patients) and JAK2 with MPL (4 patients). Compared with the single-driver group, the dual-driver group had a significantly higher risk of bleeding [4.1% (8/194) vs. 33.3% (3/9), P = 0.008] and a higher proportion of uncommon mutations [3.6% (7/194) vs. 33.3% (3/9), P = 0.006]. No statistically significant differences were observed between the two groups regarding age, thrombosis incidence, splenomegaly, or routine blood test indicators. During follow-up, 1 patient in the dual-driver group died from cerebrovascular disease. No leukaemia transformation or disease-related deaths occurred among the remaining patients. DISCUSSION:The increased bleeding risk in dual-driver patients may be related to a higher proportion of CALR mutations, elevated platelet counts, and higher variant allele frequencies, though these findings require validation in larger cohorts due to the small sample size. The higher prevalence of uncommon mutations suggests a more complex mutational landscape in this subgroup. CONCLUSION:Patients with Ph-negative MPN and dual-driver gene positivity may have a higher risk of bleeding and a more complex gene mutation profile.
OBJECTIVES:Talquetamab (G-protein-coupled receptor class C group 5 member D [GPRC5D] × CD3 bispecific antibody) demonstrated antitumor activity in relapsed/recurrent multiple myeloma (RRMM) in the phase I/II MonumenTAL-1 study. We report the safety profile of talquetamab in Chinese patients from MonumenTAL-1, focusing on GPRC5D-associated on-target/off-tumor adverse events (AEs). METHODS:Adult Chinese patients with heavily pretreated RRMM and measurable disease received subcutaneous talquetamab 0.4 mg/kg once weekly (QW) or 0.8 mg/kg biweekly (Q2W). Incidence, time to onset, duration, and recovery status of GPRC5D-associated AEs were reported. Data cutoffs: 29 February 2024 (QW cohort); 26 August 2024 (Q2W cohort). RESULTS:A total of 41 adult Chinese patients were included in this study (QW cohort, n = 29; Q2W cohort n = 12). Median treatment duration was 7.7 months (QW cohort) and 7.1 months (Q2W cohort); median follow-up was 16.3 and 13.9 months, respectively. GPRC5D on-target/off-tumor AEs, predominantly grade 1-2 (one grade 3 non-rash skin toxicity; QW cohort), were most commonly oral AEs (dysgeusia, dry mouth), skin AEs (rash, non-rash skin toxicity), and nail disorders; 50%-100% resolved by data cutoff. AEs were managed with supportive therapies. Talquetamab dose modification was needed in one case (grade 2 weight decrease). DISCUSSION:The generally mild GPRC5D-associated AEs were well tolerated and consistent with the known safety profile of talquetamab. Supportive management of these AEs without need for dose modification enabled prolonged treatment. CONCLUSIONS:Education of patients with RRMM on potential GPRC5D-associated AEs before starting treatment, and timely management upon experience, may ensure optimum exposure and thus maximum benefit with talquetamab.
OBJECTIVE:To identify clinical factors associated with repeat platelet (PLT) transfusion among thrombocytopenic patients and develop an exploratory relative-risk stratification framework for repeat transfusion during hospitalization. METHODS:This retrospective case-control study included thrombocytopenic inpatients who received at least one PLT transfusion. Patients with repeat transfusion (≥2 transfusions during the same hospitalization, n=145) were compared with those receiving a single transfusion (n = 145). Multivariable logistic regression using clinically prespecified predictors was performed, with ten-fold cross-validated LASSO used to assess variable stability. Model performance was evaluated by AUC, calibration measures, Brier score, and 1,000-resample bootstrap optimism correction. A simplified integer-based score was developed. RESULTS:Multivariable analysis identified hematologic malignancy, active bleeding, splenomegaly, lower PLT and hemoglobin levels, absence of thrombopoietic-agent use before the first transfusion, and transfusion timing as factors associated with repeat PLT transfusion. The primary model demonstrated an apparent AUC of 0.805 (95% CI, 0.756-0.855), with a bootstrap-corrected C-index of 0.777. The corrected Brier score was 0.196, and the bootstrap-corrected calibration intercept and slope were 0.001 and 0.860, respectively. The simplified score (0-12 points) stratified patients into low-, medium-, and high-score groups, with observed repeat transfusion proportions of 20.0%, 50.7%, and 83.8%, respectively (trend χ2 = 59.904, P < 0.001). CONCLUSION:Several clinical factors were associated with repeat PLT transfusion. The proposed score may support exploratory relative-risk stratification within the development sample; external validation is required before estimating absolute risk or clinical implementation.
Introduction Viral infection serves as an important precipitating factor for AIHA, and patients undergoing treatment remain susceptible to such infections.Objectives This review focuses on the effects of viral infection on AIHA pathogenesis, infection risks associated with treatment, and preventive strategies.Methods Literature review method.Results Viruses mainly induce autoimmune hemolytic anemia (AIHA) through direct adsorption, molecular mimicry, and cytokine secretion. During treatment, patients with AIHA are susceptible to viral infections and reactivation of pre-existing viruses due to immunosuppression.Discussion It points out that clinical practice currently lacks standardized prevention, control, and treatment protocols for virus-associated AIHA, and there are no unified guidelines. Further in-depth basic and clinical research is required in the future to elaborate on the mechanisms linking viral infection and AIHA in detail, laying a foundation for subsequent systematic clinical diagnosis and treatment.Conclusion Viral infection is a significant risk factor influencing morbidity and mortality in AIHA patients. During clinical management, vigilant monitoring of common viral infections and their potential reactivation is warranted, and prophylactic antiviral strategies may be considered.
OBJECTIVES:To develop an individualized nomogram for predicting disease progression risk in systemic anaplastic large cell lymphoma (sALCL). METHODS:Independent predictors of progression-free survival (PFS) were identified using Cox regression in a multicenter retrospective cohort of 109 sALCL patients (2010-2022). These were incorporated into a three-factor nomogram, evaluated via bootstrapped internal validation (1000 resamples), ROC analysis, C-index, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS:A total of 29 PFS events occurred during a median follow-up of 31 months. Multivariable modelling selected serum β2-microglobulin elevation, extranodal disease, and front-line chemotherapy choice (CHOP versus CHOPE or BV+CHP) as autonomous progression drivers. Upon internal bootstrap validation, the nomogram yielded strong prognostic accuracy, achieving AUCs of 0.81, 0.85 and 0.87 for 1-, 3- and 5-year progression-free survival, alongside a corrected C-index of 0.779 (95% CI: 0.699 - 0.861). Calibration plots showed close agreement between predicted and observed outcomes, while DCA confirmed superior net clinical benefit versus conventional IPI or Ann Arbor stratification across multiple decision thresholds. CONCLUSION:This first sALCL-specific nomogram integrates clinical and treatment variables to provide personalized PFS risk estimation. While internally validated, this exploratory, observation-based tool requires external validation and recalibration in prospective cohorts before clinical implementation.
OBJECTIVES:Low bone mass is common in adults with transfusion-dependent thalassemia (TDT). While sarcopenia contributes to frailty, studies examining its association with falls and fractures in TDT remain limited. This study aimed to determine the prevalence of probable sarcopenia in adults with transfusion-dependent thalassemia and to identify related risk factors. METHODS:This cross-sectional study included 45 adult TDT patients followed at Bursa City Hospital Hematology Clinic between September 2023 and September 2024, and 40 age- and sex-matched healthy controls. Bone mineral density (BMD) was assessed per Turkish Endocrinology Osteoporosis Guidelines and classified as normal, osteopenia, or osteoporosis. Probable sarcopenia was evaluated according to EWGSOP2 criteria based on handgrip strength measurements[14]. Anthropometric data and biochemical parameters were recorded. RESULTS:Eighty-five participants (52.9% TDT, 47.1% controls) were evaluated. The mean BMI was 21.6 ± 1.99 kg/m2. No significant differences were observed in calcium, vitamin D levels (p = 0.492, p = 0.068, p = 0.911, respectively). Handgrip strength was significantly lower in TDT patients (24.96 ± 12.75 kg) than in controls (33.9 ± 15.39kg; p = 0.004). Probable sarcopenia was identified in 13.3% of patients and in none of the controls (p = 0.027). DISCUSSION:Routine screening for probable sarcopenia should be incorporated into fracture prevention strategies for TDT, particularly among osteoporotic individuals. Therefore, the findings of this study should be interpreted as exploratory observations rather than confirmatory evidence. CONCLUSION:Probable sarcopenia was identified in a subset of adult patients with TDT based on reduced handgrip strength according to EWGSOP2 criteria. Future longitudinal and multicenter studies incorporating muscle mass and functional performance measurements are required to confirm these findings.
OBJECTIVE:Gastrointestinal bleeding (GIB) is a major cause of morbidity in von Willebrand disease (vWD), most commonly resulting from angiodysplasia. Current obscure gastrointestinal bleeding (OGIB) algorithms are primarily anatomy-based and often overlook underlying hemostatic disorders, delaying diagnosis and promoting recurrent bleeding. This review summarizes current evidence on the molecular basis, diagnosis, and management of vWD-associated GIB and proposes a mechanism-oriented diagnostic framework. METHODS:A comprehensive narrative review of experimental, translational, and clinical studies was conducted, focusing on inherited vWD, acquired von Willebrand syndrome (AvWS), gastrointestinal angiodysplasia, endothelial biology, and diagnostic and therapeutic strategies. RESULTS:Deficiency or dysfunction of high-molecular-weight von Willebrand factor (vWF) multimers promotes angiodysplasia by disrupting Weibel-Palade body homeostasis, enhancing Ang-2/Tie2 and VEGF signaling, impairing integrin αvβ3 function, and fostering pro-inflammatory endothelial activation. Genetic and epigenetic modifiers, including FLI1, STXBP5, ABO blood group, and miR-24, further influence vascular susceptibility. Based on these mechanisms, we propose a four-stage diagnostic framework integrating bleeding assessment, platelet function screening, and targeted vWF testing with conventional endoscopic evaluation to facilitate earlier recognition of vWD/AvWS in patients with recurrent or obscure GIB. This strategy supports mechanism-based treatment combining hemostatic replacement therapies with selected anti-angiogenic approaches. CONCLUSION:vWD-associated GIB should be regarded as a systemic vascular-hemostatic disorder rather than an isolated structural gastrointestinal disease. Integrating hemostatic evaluation into OGIB pathways may improve diagnostic accuracy, reduce unnecessary procedures, and enable personalized management of patients with recurrent bleeding.
OBJECTIVE:Acute myeloid leukemia (AML) is a severe and life-threatening malignant disease of the hematopoietic system. Our previous research found that ANP32B is regulated by super enhancers in pediatric AML and regulates the progression of AML by modulating histone H3K27ac. Using virtual screening technology, we discovered that Raloxifene may be a small-molecule inhibitor targeting ANP32B. METHODS:Proliferation and apoptosis analysis were used to evaluate the effect of Raloxifene on AML cells. By establishing a xenograft model in NSG mice, 10.0 mg/kg of Raloxifene or a control solvent was intraperitoneally injected into the mice daily, and the tumor progression was monitored. Additionally, RNA sequencing, qRT‒PCR and WB were used to measure gene expression levels after Raloxifene treatment. RESULTS:The CCK-8 assay showed the IC50 value of Raloxifene in AML cells. The number and size of colony-forming AML cells treated with Raloxifene significantly decreased, and cell apoptosis increased in a dose-dependent manner. The fluorescence values in NSG mice treated with Raloxifene was significantly lower than control group. RNA sequencing revealed that Raloxifene inhibited the expression of the MYC pathway genes in MV4-11 cells. CONCLUSION:Raloxifene exhibits anti-AML activity both in vitro and in vivo. By targeting ANP32B, Raloxifene effectively inhibits the proliferation of AML cells, induces cell apoptosis, and reduces the expression of C-MYC. Raloxifene may potentially serve as a candidate drug for the treatment of acute myeloid leukemia.
OBJECTIVE:This study was initiated to resolve a discrepancy between conventional genetic findings and clinical presentation in a proband with α-thalassemia. The initial genotype (-α4.2/-α4.2) was inconsistent with the Hb H disease phenotype, suggesting the presence of an undetected pathogenic variant. METHODS:To characterize the underlying genetic defect, we employed a multi-technique approach. The proband's DNA was analyzed using multiplex ligation-dependent probe amplification (MLPA), third-generation sequencing (TGS), and copy number variation sequencing (CNV-seq). Prenatal diagnosis was performed because the husband carried the --SEA/αα genotype. RESULTS:Investigations revealed a novel, large deletion on the α-globin gene cluster. Unlike MLPA and TGS, which indicated a deletion but could not precisely define its breakpoints due to its telomeric location, CNV-seq successfully mapped the deletion to chr16:97840-230167. This represents a 132,327 bp (132 kb) deletion, which we designated the 'Dongxing' (--DX) deletion. The proband's corrected genotype was confirmed as --DX/-α4.2. Prenatal diagnosis revealed the fetus had Hb H disease (--SEA/-α4.2). CONCLUSIONS:We identified and characterized a novel α-thalassemia deletion (Dongxing deletion) using CNV-seq. This case highlights the limitations of conventional genotyping and underscores the importance of comprehensive genetic analysis in cases of genotype-phenotype discrepancy.
OBJECTIVES:Terminal complement inhibitors can control intravascular hemolysis in Paroxysmal Nocturnal Hemoglobinuria (PNH) patients, although the hematological response achieved may not persist, and it may become unsatisfactory. The proximal (C3) complement inhibitor Pegcetacoplan (PEG) improves this situation in clinical trials, yet real-world data on its efficacy and safety are scarce. METHODS:This non-interventional, retrospective, multicenter study presents clinical and hematological data from the first PNH patients in Spain treated with PEG (n = 32, median 13 months, range 4-61). RESULTS:PEG rapidly increases the patient's hemoglobin (median increase of 2.65 g/dL in 4 weeks, > 2 g/dL increase in 56.3% of patients), reaching > 8, 10 and 12 g/dL in 93.7%, 87.5% and 46.9% of patients, respectively. Packed red blood cell transfusion requirements dropped from 62.5% to 15.6% of patients treated with PEG, and there was a fall in breakthrough hemolysis from 34.4% to 9.4% after 6 months of treatment. No thrombosis and only mild adverse events (n = 11 patients) were described with PEG therapy. Finally, physicians perceived important enhancements in patients' health-related quality of life. DISCUSSION:This real-world clinical data confirms that PEG produces significant and rapid improvements in hemoglobin and hemolytic parameters, with a favorable safety profile. The data extends that of earlier clinical trials and small real-world studies by offering a longitudinal (as opposed to cross-sectional) assessment of the patient responses across a large number of centers, following a variety of clinical practices.. CONCLUSION:PEG treatment of patients with PNH produces significant and rapid improvements in hemoglobin and hemolytic parameters, with a favorable safety profile.
Background Myelofibrosis (MF) includes primary myelofibrosis (PMF) and secondary myelofibrosis (SMF) evolving from essential thrombocythemia (ET) or polycythemia vera (PV). The clinical and molecular heterogeneity of MF remains incompletely characterized in real-world cohorts.Methods We retrospectively analyzed 56 patients with MF treated at a single center, including 33 with PMF and 23 with SMF (ET-MF or PV-MF). Clinical characteristics, laboratory parameters, bone marrow pathology, cytogenetic and molecular findings, treatment strategies, and follow-up outcomes were evaluated.Results PMF patients demonstrated a predominantly cytopenic phenotype, characterized by more severe anemia and lower platelet counts, whereas SMF patients showed a more proliferative profile with higher leukocyte and platelet counts. Bone marrow examination revealed typical megakaryocytic atypia and reticulin fibrosis in both groups, while PMF exhibited more heterogeneous marrow cellularity. Mutational analysis showed that JAK2 was the most frequent driver mutation, followed by CALR and MPL, and approximately one-third of PMF cases were triple-negative. Among additional mutations, ASXL1 was the most common, followed by spliceosome-related genes such as SF3B1 and U2AF1. Patients harboring JAK2 mutations displayed higher hemoglobin levels, red blood cell counts, and neutrophil percentages compared with JAK2-wild type patients. Treatment strategies included supportive care, interferon, hydroxyurea, and ruxolitinib. During follow-up, most patients remained alive, although leukemic transformation occurred in a small proportion of PMF cases.Conclusions PMF and SMF demonstrate distinct clinical phenotypes despite sharing bone marrow fibrosis as a common endpoint. The mutational landscape highlights the genetic heterogeneity of MF and underscores the importance of integrating clinical, pathological, and molecular information to improve disease characterization and guide individualized management.
Objectives To evaluate the efficacy and safety of sirolimus-based treatment regimens in patients with antinuclear antibody (ANA)-positive immune thrombocytopenia (ITP).Methods This retrospective single-center study enrolled patients with a clear clinical diagnosis of ANA-positive ITP. They were divided into two groups based on different treatment regimens: the sirolimus monotherapy group (SRL group) and the sirolimus plus dexamethasone combination group (combination group).Results During treatment, the combination group achieved the initial overall response (ORR) significantly faster than the SRL group (p < 0.05); additionally, in the early treatment phase (Week 1, Week 4), there were statistically significant differences in efficacy between the two groups, while no statistically significant difference in efficacy was observed during subsequent follow-up. Regarding treatment safety, all adverse events were Grade 1-2; no Grade 3 or higher adverse events were reported and no treatment-related deaths occurred. The most frequently observed adverse events were oral ulcers, gastrointestinal distress, and elevated liver enzymes. There was no statistically significant difference in the total incidence of adverse events between the two groups.Conclusion In this retrospective single-center study, sirolimus-based regimens showed favorable efficacy and acceptable safety in ANA-positive ITP. Adding dexamethasone to sirolimus led to faster initial responses versus sirolimus alone, though no significant difference was seen in follow-up. These findings support the feasibility and potential efficacy of sirolimus-based regimens in ANA-positive ITP, warranting prospective controlled studies.
OBJECTIVES:Major depressive disorder (MDD) and venous thromboembolism (VTE) frequently co-occur and impose substantial public health burdens. Previous Mendelian randomization (MR) studies examined their causal association but were limited to European (EUR) ancestry. This study utilizes trans-ethnic MR (TEMR) to address this limitation. METHODS:MDD data for EUR, African (AFR), Hispanic (HIS), East Asian (EAS), and South Asian (SAS) ancestries were obtained from the Psychiatric Genomics Consortium (PGC). VTE discovery and replication datasets were provided by the Global Biobank Meta-analysis Initiative and Million Veteran Program. Independent genome-wide significant variants (P < 5 × 10-8) served as instrumental variables. The Nelder-Mead simplex algorithm was the primary optimizer in the TEMR framework, with EUR ancestry as auxiliary population. Validation included BFGS, CG, L-BFGS-B, and SANN. Sensitivity analyses comprised MRLap, the Steiger test, and assessments of heterogeneity and pleiotropy. RESULTS:Validation confirmed bidirectional causal associations between MDD and VTE in EUR ancestry (OR > 1, P < 0.05). Forward TEMR showed genetically predicted MDD increased VTE risk in AFR ancestry (OR: 1.241, 95% CI: 1.149-1.340, P = 0.019). Reverse analysis indicated genetically predicted VTE increased MDD risk in EAS (OR: 1.014, 95% CI: 1.013-1.015, P = 8.74×10-16), SAS (OR: 1.078, 95% CI: 1.044-1.113, P = 0.028), AFR (OR: 1.076, 95% CI: 1.074-1.078, P = 2.51×10-109), and HIS (OR: 1.123, 95% CI: 1.111-1.134, P = 8.41×10-6) ancestries. Sensitivity and validation analyses supported robustness. CONCLUSION:This TEMR study enhanced detection power by identifying increased MDD risk in EUR and AFR ancestries. It established a causal link from VTE to elevated MDD risk across all five ancestries, underscoring ancestry heterogeneity and improving generalizability.
BACKGROUND:ABO hemolytic disease of the newborn (ABO-HDN) is a major cause of hyperbilirubinemia in neonates, often inducing significant elevation of serum bilirubin levels shortly after birth. PURPOSE:This study aimed to assess the prognostic value of Aquaporin 1 (AQP1) for hyperbilirubinemia in ABO-HDN as reflected by the duration of phototherapy, a key clinical indicator of disease severity and treatment response. METHODS:A retrospective cohort study was conducted, enrolling 168 neonates with ABO-HDN-related hyperbilirubinemia. Serum AQP1 expression was detected by RT-qPCR, and neonates were divided into a high-AQP1 expression group (n = 84) and a low-AQP1 expression group (n = 84) according to the median. All neonates were followed up for 7 days after the initiation of phototherapy, and a cure was defined as no total bilirubin (TBIL) rebound within 48 h after reaching the normal TBIL level. The cure rate was defined as the proportion of participants who achieved a cure within the 7‑day follow‑up period. RESULTS:The AQP1 expression in the ABO-HDN group was significantly higher than that in the control group. Additionally, the high-AQP1 group had a longer cure time and a lower cure rate within 7 days. Spearman analysis showed that AQP1 was positively correlated with TBIL (R = 0.481, P < 0.001). Cox regression analysis confirmed that high AQP1 expression was associated with a reduced cure rate (HR = 0.623, 95%CI: 0.449-0.861, P = 0.004). CONCLUSION:High-AQP1 expression was closely associated with prolonged treatment duration in ABO-HDN-related hyperbilirubinemia. AQP1 can serve as a potential molecular marker for prognostic assessment and individualized treatment guidance in such neonates.
OBJECTIVES:Lactylation and liquid-liquid phase separation related genes have been reported to be associated with tumor prognosis and immunity, but their specific influence on the prognosis and immune characteristics of diffuse large B-cell lymphoma (DLBCL) remains unclear. METHODS:GSE56315 (33 control samples and 55 DLBCL patient samples) has been used to screen for lactylation and liquid‒liquid phase separation related differentially expressed genes (LLRDEGs). Based on the optimal cutoff, LLRDEGs associated with DLBCL prognosis (overall survival) was further screened through LASSO and univariate Cox regression. Then, based on the GSE10846 dataset (414 DLBCL samples), a prognostic model was constructed based on the LLRDEGs. The Kaplan-Meier curve is used to evaluate the prognostic value (median risk score). And validate the prognostic model on an independent external validation dataset (GSE181063 (1310 DLBCL samples)). Finally, further analysis was conducted on consensus clustering, biological pathways, the immune microenvironment and drug sensitivity. RESULTS:4 LLRDEGs were ultimately identified as genes associated with the DLBCL' prognosis. A prognostic model was constructed based on the 4 LLRDEGs. An independent external validation dataset confirmed the prognostic model's prognostic value. 4 LLRDEGs were significantly correlated with various immune cells. DISCUSSION:This study screened four LLRDEGs significantly associated with prognosis and constructed a prognostic risk stratification model. The Kaplan-Meier curve confirms the prognostic value of the prognostic risk stratification model. This prognostic model is related to the clinical characteristics and immune microenvironment of DLBCL patients. CONCLUSION:This study elucidates the role of LLRDEGs in the prognosis and immune features of DLBCL, providing insights into potential therapeutic targets.
Objectives Pediatric acute myeloid leukemia (AML) is biologically distinct from adult AML and carries a poor prognosis. OVCA2, a serine hydrolase with context-dependent roles, has unknown function in AML. We aimed to investigate its role, regulation, and clinical significance in pediatric AML.Methods OVCA2 was identified as a downstream target of a pediatric AML-specific core transcriptional regulatory circuit using CUT&Tag integrative analysis. Expression and prognostic associations were assessed in TARGET (pediatric) and TCGA (adult) datasets. Functional validation via lentiviral shRNA knockdown was performed in MV4-11 and Kasumi-1 cells using CCK-8, colony formation, and cell cycle assays. RNA-seq and GSEA elucidated mechanisms. Co-knockdown of CDKN1A tested functional rescue.Results OVCA2 was significantly upregulated in AML and correlated with worse overall survival exclusively in the pediatric cohort. Knockdown impaired proliferation, colony formation, and induced G1 arrest, with reduced C-MYC and CDK2 levels. Transcriptomic analysis revealed activation of ‘Negative Regulation of Cell Population Proliferation’ pathway, with CDKN1A as a top upregulated gene. Co-knockdown of CDKN1A partially rescued the anti-proliferative effect.Discussion OVCA2 acts as a novel oncogene in pediatric AML by transcriptionally repressing CDKN1A to drive cell cycle progression. Its age-specific prognostic association and origin from a pediatric AML core regulatory circuit highlight its role in age-related regulatory networks.Conclusion OVCA2 represents a promising therapeutic target in pediatric AML, with its effects mediated through CDKN1A repression.
Objectives Hemoglobin (Hb) variants are a common type of single-gene disorder and a frequent source of interference in HbA1c testing. Here, we first report a rare Hb variant, Hb Norton [HBA2:c.217C>G], in the Chinese population.Methods and results A 38-year-old man presented with a normal clinical and hematological phenotype. He was suspected of carrying an Hb variant following an HbA1c measurement using a high-performance liquid chromatography (HPLC) method (Bio-Rad D100), which resulted in an extremely high value of 20.24%. HbA1c was reanalyzed using a capillary electrophoresis (CE) method (Capillarys3 TERA) and a boronate affinity HPLC system (Premier Hb9210), and the results were 5.49% and 5.60%, respectively. Hemoglobin analysis by CE and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) revealed a variant peak with a mass-to-charge ratio (m/z) = 10105 Da. Sanger sequencing confirmed the presence of a rare Hb variant, Hb Norton [HBA2:c.217C>G]. It was conclusively confirmed that the co-elution of Hb Norton and HbA1c components led to the falsely elevated HbA1c values.Conclusions Some rare variants can severely affect HbA1c analysis. When encountering abnormally high values that are difficult to explain, one should consider whether variant interference is present.
