Hematology最新文献

Objectives: The aim of this study was to characterize the clinical features and outcomes of patients with JAK2 V617F- and CALR-unmutated essential thrombocythemia (ET) and to identify potential driver mutations through whole-exome sequencing (WES).

Methods: This was a cross-sectional study including patients diagnosed with ET between 2007 and 2024. Clinical characteristics and outcomes were compared between patients with and without JAK2V617F and CALR mutations. WES was analyzed in JAK2V617F- and CALR-unmutated ET patients.

Results: Thirty-nine out of 162 ET patients (24%) were JAK2V617F- and CALR-unmutated. This group was younger than patients in the JAK2V617F mutated group (mean age 53.7 vs. 61.1 years, p = 0.012) and had lower incidence of thrombotic events (5.1% vs. 9.1%, p = 0.327). The median overall survival was 13.51 years compared to 12.61 years in patients with JAK2V617F or CALR mutations (p = 0.63). There were no statistically significant differences in clinical symptoms, incidence of thrombosis, bleeding, myelofibrosis, or leukemic transformation. WES was analyzed in 15 patients. Uncommon MPL mutations were identified, including MPLL265F, MPLP70L, and MPLR321Q. Potential novel CALR mutations were detected in exon 5 (c.540C > T, N180 = ) and exon 6 (c.703-3del). Non-driver gene mutations were detected, including RUNX1 (57.1%), ASXL1, DNMT3A, SETBP1, and MSH6.

Discussion and conclusions: Patients with JAK2V617F- and CALR-unmutated ET tend to present at a younger age and exhibit a lower incidence of thrombosis compared to those with JAK2V617F-mutated ET. The application of WES enabled the detection of uncommon and potential driver mutations in JAK2V617F- and CALR-unmutated ET.

Objectives: Limited published data exist on switching therapy from pegcetacoplan to iptacopan in patients with paroxysmal nocturnal hemoglobinuria (PNH).

Methods: Three patient cases were collected from the Mayo Clinic, Cleveland Clinic, and Levine Cancer Institute.

Results: Patient 1 is a 57-year-old woman with PNH. She experienced extravascular hemolysis (EVH) while on C5 inhibitors and breakthrough hemolysis (BTH) after switching to pegcetacoplan. Patient 2 is a 37-year-old woman seeking care for PNH, who was initiated on C5 inhibitor therapy and switched to pegcetacoplan. EVH and BTH were observed while she was on C5 inhibitor therapy, and transfusions were required with both C5 inhibitor and pegcetacoplan therapy. Patient 3 is a 58-year-old man with aplastic anemia and PNH who was initiated on C5 inhibitor therapy, then switched to pegcetacoplan. He experienced both EVH and BTH.

Discussion: All three patients switched from pegcetacoplan to iptacopan, and none experienced EVH or BTH while on iptacopan. After switching to iptacopan, all three patients improved hemoglobin levels and abating transfusion requirements.

Conclusion: In this case series, three patients with PNH were successfully transitioned from pegcetacoplan to iptacopan monotherapy. No patients exhibited laboratory evidence of BTH, EVH, or intravascular hemolysis after switching to iptacopan.

Objectives: Our study integrates SNP array and metaphase cytogenetics (MC) to decode clonal architecture in myelodysplastic syndromes (MDS) and related disorders.

Methods: We retrospectively analyzed chromosomal aberrations in 33 patients diagnosed with MDS and related disorders by both SNP array and MC, of whom ten were detected with chromosomal copy number variations (CNVs) by MC. SNP array was used to quantify the clonal burden of CNVs using the metric median copy number state.

Results: We found that SNP array-derived median copy number state was associated with the abnormal/total ratio by MC, implying the utility of the SNP array derived indicator for detecting the clonal burden of chromosomal CNVs in MDS and related disorders. In our cohort, patients with isolated trisomy 8 clones showed relatively low clonal burden and more stable outcomes compared with those having trisomy 8 in complex karyotypes, whereas +1/1q + clones, even as sole lesions, were associated with aggressive progression. The higher clonal burden of trisomy 8 (elevated median copy number deviations compared to other lesions) was found in patients with complex karyotypes and poor prognosis, which further supported the staged evolution theory and provided a new perspective for studying the development of chromosomal abnormalities in myelodysplastic neoplasms.

Conclusion: The SNP array may serve as a novel tool for precision disease management, enabling early identification of high-risk clones and refinement of prognostic assessment in myelodysplastic neoplasms.

Objective: To analyze the clinical characteristics and prognosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV⁺DLBCL) in a Chinese cohort.

Methods: Fifty-seven EBV⁺DLBCL patients (diagnosed between 2013 and 2020) and 228 EBV-negative DLBCL (EBV^-DLBCL) controls were included. Differences were compared and prognostic factors were identified using univariate and multivariate analysis.

Results: EBV⁺DLBCL patients (median age, 56 years; 38 men [66.7%]) predominantly had non-GCB origin (70.2%). Compared with EBV^-DLBCL, EBV⁺DLBCL patients more frequently presented with B symptoms, hypoalbuminemia, anemia, >1 extranodal site involvement, and elevated LDH andβ2-microglobulin (all P < 0.05). The common extranodal sites were the digestive tract (stomach), nasopharynx, bone marrow, and bone. CD30 positivity was higher in EBV⁺DLBCL patients (42.1% vs. controls, P < 0.001). After R-CHOP-like therapy, EBV⁺DLBCL patients achieved complete and overall response rates of 55.5% (30/54) and 83.3% (45/54), respectively. With a median follow-up period of 28 months, the relapse rate was 22.2% (10/45). The response and relapse rates were similar between groups. Multivariate analysis identified elevatedβ2-microglobulin and bone marrow invasion as independent risk factors for worse progression-free survival (PFS), and elevatedβ2-microglobulin plus decreased hemoglobin for worse overall survival (OS) in EBV⁺DLBCL.

Conclusion: EBV⁺ DLBCL in this Chinese cohort was primarily non-GCB. Elevatedβ2-microglobulin and bone marrow invasion independently predicted inferior PFS, while elevatedβ2-microglobulin and anemia predicted inferior OS.

Purpose: Platinum-based chemotherapy is considered as salvage therapy to relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients. However, treatment failure due to drug resistance occurs in some patients, particularly those with Exportin 1 (XPO1) overexpression. This study investigates whether XPO1 inhibition enhances platinum sensitivity in DLBCL subtypes.

Methods: XPO1 expression in DLBCL was predicted using online datasets. Cell lines representing DLBCL subtypes were treated with varying concentrations of the XPO1 inhibitor selinexor (XPO1i), cisplatin (CDDP), and oxaliplatin (OXA), alone or in combination. Cellular viability was assessed via CCK-8 assay, while apoptosis rates and reactive oxygen species (ROS) levels were measured by flow cytometry. Protein levels of XPO1 and pro-apoptotic cytokines were evaluated using Western blotting.

Results: Bioinformatic analysis revealed elevated XPO1 expression in DLBCL. Both XPO1i and platinum-based therapy inhibited cellular viability and promoted apoptosis across DLBCL subtypes in a dose-dependent fashion. The combination of XPO1i at its IC50 and CDDP synergistically suppressed cell viability across both activated B-cell-like- and germinal-center B-cell-like (GCB)-DLBCL subtypes compared to CDDP monotherapy. The combination of XPO1i at its IC30 and OXA synergistically led to a greater reduction in cell viability, along with enhanced induction of apoptosis and ROS accumulation in GCB-DLBCL cells. In OCI-Ly8 and OCI-Ly1 cells, OXA alone inhibited phosphorylation of AKT and mTOR while increasing phosphorylation of JNK, ATM, and p53, and expression of γH2AX; these effects were potentiated by the combination of XPO1i and OXA.

Conclusion: XPO1 inhibition enhances platinum-induced cytotoxicity in GCB-DLBCL, supporting clinical evaluation of XPO1i-platinum combinations as salvage therapy.

Objectives: Numerous observational research avenues have identified a possible correlation between aplastic anemia and autoimmune diseases, rooted in analogous dysfunctional immune responses. Nevertheless, causal link between autoimmune diseases and aplastic anemia remains elusive. The study aims to investigate the causal association of autoimmune diseases and aplastic anemia.

Methods: This study leveraged summary data from genome-wide association studies pertaining to six prevalent autoimmune diseases: ulcerative colitis, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, celiac disease, and type 1 diabetes mellitus, procured from expansive, public genome-wide association studies meta-analysis databases. Aplastic anemia - related genetic information was extracted from the UK Biobank. Utilizing single nucleotide polymorphisms as genetic instruments - meeting criteria P < 5 × 10^-8 and linkage disequilibrium [LD] r² < 0.001 - the study employed Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis to gauge the sensitivity concerning the impact of autoimmune diseases on aplastic anemia.

Results: The findings underscore a definitive causal relationship between systemic lupus erythematosus and aplastic anemia, as evidenced by the statistics (OR_IVW = 1.193, 95% CI 1.013-1.404, P = 0.035). Duplicate SLE GWAS from the FinnGen database demonstrated that patients with SLE are more susceptible to AA (OR_IVW = 1.193, 95% CI 1.013-1.404, P = 0.035). Additionally, the Mendelian randomization analysis reported no evidence of horizontal or directional pleiotropy.

Conclusions: In summary, the study suggests that systemic lupus erythematosus could serve as a potential risk factor contributing to the onset of aplastic anemia. To substantiate this hypothesis, ensuing studies encompassing larger sample sizes are warranted.

Objectives: Acute myeloid leukemia (AML) is an aggressive hematological malignancy with poor prognosis. Abnormal energy metabolism is a well-recognized cancer hallmark, yet the role of energy metabolism-related genes (EMRGs) in AML remains unclear. Thus, this study aims to identify such hub genes in AML and explore their prognostic significance, related pathways, and therapeutic targeting potential.

Methods: AML-related datasets and EMRGs were obtained from public databases. The hub gene was identified through differential expression analysis, correlation analysis and PPI analysis, etc. Then, a set enrichment analysis was conducted. A drug-gene network was constructed, and immune microenvironment analysis was performed.

Results: In this study, six hub genes (CDH1, AGRN, NDST3, GPC3, CD44, and COL4A1) were identified, and their expression levels were significantly associated with the overall survival of AML patients. These hub genes also exhibited significant expression differences among clusters; for instance, CD44 was upregulated in cluster 2, while COL4A1 and GPC3 were downregulated. Functional enrichment analysis showed that they were associated with 'ribosome', ECM-receptor interaction', and other functional pathways. Consequently, lapatinib, gentamicin, etc., were predicted based on the hub genes, and we found that CDH1 was positively correlated with multiple cells, such as NK cells and T cells, and there was the highest positive correlation between CDH1 and NK cells.

Discussion: AML shows a poor response to chemotherapy. Six hub genes linked to metabolism, pathways (ribosome, immune, NOD), and drug targets (e.g. Lapatinib/CDH1) were identified. Correlation of CDH1 with NK cells is discussed.

Conclusion: These hub genes offer promising targets for future individualized AML therapy.

Objective: This study aimed to investigate the therapeutic potential of sovleplenib, a selective SYK inhibitor, in aplastic anemia (AA), focusing on its effects on immune modulation and the cGAS-STING-NF-κB inflammatory axis.

Methods: An immune-mediated AA mouse model was established and treated with sovleplenib. Hematopoietic function was assessed via peripheral blood counts and bone marrow mononuclear cell (BMNC) counts. Immune cell profiles were analyzed by flow cytometry. Cytokine levels were measured by ELISA. Underlying mechanisms were explored through proteomics and Western blotting.

Results: Sovleplenib treatment significantly improved peripheral blood counts (HGB, WBC, PLT) and BMNCs, and reduced bone marrow fat vacuolation. It corrected immune imbalance by increasing the CD4⁺/CD8⁺ T-cell ratio and decreasing the M1/M2 macrophage ratio, promoting an M2 phenotype. Concurrently, it elevated Arg-1 level while suppressing ROS, TNF-α, and IFN-β. Mechanistically, sovleplenib inhibited the activation of key pathway components (cGAS, STING, p-TBK1, p-p65).

Discussion: The results demonstrate sovleplenib's dual role in promoting hematopoiesis and immunomodulation. Its efficacy is mechanistically linked to the suppression of the overactivated cGAS-STING-NF-κB pathway, a key driver of inflammation in AA.

Conclusion: Sovleplenib represents a promising targeted therapy for AA.

Objective: To report a case of severe immune-mediated thrombocytopenia highly suspected to be induced by propofol and/or etomidate.

Clinical features: A 62-year-old female patient developed acute, severe thrombocytopenia following two separate general anesthesia events in 2025. The first episode occurred 14 days after laparoscopic renal cyst unroofing, with a platelet nadir of 1 × 10⁹/L. The second episode occurred 11 days after painless gastroscopy and colonoscopy, with a platelet nadir of 2 × 10⁹/L. Platelet counts normalized after treatment with glucocorticoids, thrombopoietin receptor agonists, and platelet transfusions on both occasions. We suspect that propofol and/or etomidate, common drugs used in both anesthesia procedures, induced immune-mediated thrombocytopenia.

Conclusion: Propofol and/or etomidate may induce immune-mediated thrombocytopenia. Anesthesiologists should enhance their awareness of this rare adverse reaction. When unexplained thrombocytopenia occurs post-anesthesia, besides common causes like sepsis, DIC, or heparin-induced thrombocytopenia, propofol and/or etomidate induced thrombocytopenia must be considered as an important differential diagnosis.

Objectives: This study investigated outcomes and response to pegcetacoplan in complement inhibitor naïve (CI_naïve) and experienced (CI_exp) PNH patients.

Methods: Data were drawn from the Adelphi PNH Disease Specific Programme™, a cross-sectional survey of physicians and their patients in Canada, France, Germany, Italy, Spain, and the UK between December 2023 and April 2024. Physicians reported patient characteristics and clinical outcomes, which were used to define pegcetacoplan response. Results were stratified by prior CI prescription. Analyses were descriptive.

Results: Forty-eight physicians reported on 63 patients (CI_naïve:11; CI_exp:52). Median (IQR) age was 45.0 (33.0-55.0) years, 60.3% were male. At treatment initiation versus at survey for CI_naïve and CI_exp, respectively, median (IQR) haemoglobin levels (g/dL) were 8.0 (5.0-9.0) versus 12.0 (11.2-12.3), and 9.0 (8.0-9.2) versus 11.0 (10.2-12.0); lactate dehydrogenase levels (U/L) were 500 (350-1625) versus 250 (175-525), and 470 (290-588) versus 265 (190-379); absolute reticulocyte counts (x10⁹ /L) were 220 (151-250) versus 110 (95-140), and 212 (134-281) versus 120 (105-228). At pegcetacoplan initiation, 4.4% of patients met criteria of good-to-complete response versus 79.5% at survey.

Conclusions: Pegcetacoplan proved effective for CI_naïve and CI_exp patients in a real-world setting, with numerically improved clinical outcomes and high response rate.