Hematology最新文献

Background: Hemoglobin (Hb) Hekinan is a prevalent α-globin variant frequently missed in thalassemia screening centers using high-performance liquid chromatography (HPLC) or capillary electrophoresis. This study aims to investigate the hematological and molecular characteristics of Hb Hekinan in a large cohort.

Methods: Hb variants were identified using isoelectric focusing (IEF) and HPLC. Hb Hekinan was confirmed by direct DNA sequencing. Additional genetic determinants, including α-thalassemia, β-thalassemia and other variants, were detected using multiplex GAP-PCR, ARMS-PCR or direct DNA sequencing as appropriate.

Results: Among 61,997 Hb typing samples, 149 cases of Hb Hekinan were identified in Thai individuals and classified into 8 genotypic groups. These included 104 Hb Hekinan heterozygotes, 10 Hb Hekinan coexisting with α⁺-thalassemia, 3 Hb Hekinan with non-deletional α-variants, 6 Hb Hekinan with α⁰-thalassemia, 21 double heterozygote for Hb Hekinan and HbE, 3 Hb Hekinan with β-thalassemia trait, 1 triple heterozygotes (Hb Hekinan/α⁰-thalassemia/Hb E) and 1 quadruple heterozygote for Hb Hekinan/α⁺-thalassemia/Hb E/Hb Hope. Hb Hekinan was well-separated from Hb A using IEF but was frequently missed with HPLC. On HPLC, Hb Hekinan could only be identified when coexisting with α⁰-thalassemia. All cases presented with either normal Hb levels or mild anemia.

Conclusions: Hb Hekinan is a prevalent α-globin variant that is often undetected by HPLC but reliably identified using IEF. These findings highlight the importance of incorporating IEF for accurate diagnosis of Hb Hekinan. Most cases are clinically benign, even when interacting with other thalassemia syndromes or Hb variants.

Objective: To evaluate the short-term efficacy and safety of eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in China.

Method: Data were retrospectively collected from patients with PNH who received at least 3 months of full-dose eculizumab. Changes in clinical and laboratory indicators after 1, 3, and 6 months of eculizumab therapy and at the end of follow-up were documented. The incidence rates of breakthrough hemolysis (BTH), extravascular hemolysis (EVH), and adverse events were recorded.

Result: A total of 48 patients, including 27 males, with a median age of 46 (12-78) years were included. Twenty-four (50%) patients had classic PNH and 24 (50%) had bone marrow failure (BMF)/PNH. Eighteen (37.5%) patients required blood transfusion. The median duration of follow-up was 6 (3-15) months. During the follow-up period, Lactate Dehydrogenase (LDH) levels were lower than those at baseline (<0.05) at all observation points. The patients showed a significant reduction in creatinine levels from baseline (P = 0.022 and P = 0.039, respectively) at 1 and 3 months. At the end of the follow-up, fifteen (83.3%) became transfusion-independent. No new thrombotic events were observed. The FACIT-Fatigue score significantly improved (P < 0.05). No significant differences were observed in the changes in hemoglobin or LDH levels between patients with classic PNH and those with BMF/PNH. BTH was observed in 17.4% of patients and EVH in 10.4%. Mild adverse events occurred in 22.9% of patients. No deaths or clonal evolution was observed.

Conclusion: Eculizumab can effectively control the hemolytic symptoms of PNH with good tolerance for Chinese patients.

Objective: This study was designed to compare treatment patterns, clinical trial participation, and clinical outcomes among patients with small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL) or Mantle cell lymphoma (MCL) by site of care.

Methods: A nationwide electronic health record (EHR)-derived de-identified database was utilized for this study. Eligible patients were diagnosed with either CLL or MCL from 2013-2022 who received systemic therapy for their disease. Overall survival (OS) was analyzed using Kaplan Meier method, censoring patients without events at last observation in the database. Cox proportional hazards regression model was used to adjust for baseline covariates.

Results: A total of 6,372 patients with CLL and 3,411 with MCL met eligibility criteria for this analysis; 13.9% and 22.2%, respectively, were treated in academic settings. Academic settings were associated with higher patient volume and were more likely to treat MCL with CAR-T, enroll patients with CLL or MCL to clinical trials, and care for patients who were younger, White, and for CLL with higher rates of del(17p) mutations (all p < 0.01). Survival was significantly longer among patients treated in academic vs community settings (median OS not reached vs 80.5 months for CLL; 95.6 vs 68.7 months for MCL from start of first-line therapy).

Discussion: Patients who received care in academic settings differed from those treated in the community; care in academic settings was associated with significantly longer OS and higher trial participation. Further research is warranted to better understand the factors that may contribute to the observed outcomes.

Background: This study aimed to develop a prognostic model based on extracellular trap-related genes (NETRGs) for patients with cALL.

Methods: Data from the TARGET-ALL-P2 and TARGET-ALL-P3 cohorts in the Genomic Data Commons database, the transcriptome dataset GSE26713, the single-cell transcriptome dataset GSE130116 from the Gene Expression Omnibus database and 306 NETRGs identified were analysed. Differentially expressed genes (DEGs) were identified from GSE26713 and differentially expressed NETRGs (DE-NETRGs) were obtained by overlapping DEGs with NETRGs. Functional analyses were conducted. Key feature genes were identified through univariate and least absolute shrinkage and selection operator (LASSO) regression. Prognostic genes were determined via multivariate Cox regression analysis, followed by the construction and validation of a risk model and nomogram. Additional analyses included immune profiling, drug sensitivity, functional differences, cell-type-specific expression, enrichment analysis and RT-qPCR.

Results: A total of 1,270 DEGs were identified in GSE26713, of which 74 overlapped with NETRGs. Seven prognostic genes were identified using univariate, LASSO and multivariate Cox regression analyses. Survival analysis revealed lower survival rates in the high-risk group. Independent prognostic analysis identified risk scores and primary diagnosis as independent predictors of prognosis. Immune cell profiling showed significant differences in cell populations such as aDCs, eosinophils and Th2 cells between risk groups. Six cell subtypes were annotated, with prognostic genes predominantly expressed in myeloid cells. RT-qPCR revealed that PTAFR, FCGR2A, RETN and CAT were significantly downregulated, while TLR2 and S100A12 were upregulated in cALL.

Conclusion: TLR2, PTAFR, FCGR2A, RETN, S100A12 and CAT may serve as potential therapeutic targets.

SUMMARYThis study systematically explored the role of NEDD8 in pediatric acute myeloid leukemia (AML) through patient sample analysis, database mining, and in vitro experiments. Our results demonstrated that NEDD8 was significantly overexpressed in newly diagnosed pediatric AML patients and was associated with poor survival outcomes. Functional enrichment analysis of the TARGET database further revealed a strong correlation between NEDD8 and cancer-related pathways. In vitro experiments showed that NEDD8 knockdown significantly inhibited the proliferation of AML cells (THP-1 and MV4-11) and induced cell cycle arrest. Collectively, these findings highlight the critical role of NEDD8 in pediatric AML pathogenesis and suggest its potential as both a prognostic biomarker and a therapeutic target.

Objective: To investigate the effects of the PI3 K inhibitor, linperlisib (YY20394), on proliferation, apoptosis, cell cycle and signaling pathways in acute myeloid leukemia (AML) cells.

Methods: The U937 cell cultures were treated with different concentrations of YY20394 to determine the IC50 value by analyzing the cell viability using Cell Counting Kit-8(CCK8). The obtained IC50 value was used for selecting the appropriate concentrations for studies on apoptosis and cell cycle changes using AO/EB dual fluorescence staining and flow cytometry respectively. The effects of YY20394 on signaling pathways at different concentrations were detected by real-time quantitative PCR (RT-PCR) and Western blotting.

Results: Compared with the control group, YY20394 significantly increased the inhibition rate of proliferation and the apoptosis rate of AML cells (P < 0.05). Treatment with 5 μM YY20394 led to cell cycle arrest predominantly in the G1phase, while 10um treatment resulted in cell cycle arrest mainly in the G2 phase. Interestingly, YY20394 did not exert its anti-leukemic effects through modulation of the PI3 K/Akt/mTOR Signaling pathway, suggesting that alternative molecular mechanisms may be involved.

Conclusion: YY20394 has a favorable inhibitory effect and significant pro-apoptotic effect on the proliferation of AML cells, which suggests that it has some potential for the treatment of AML.

Background: Ewing sarcoma breakpoint region 1(EWSR1) rearrangements have been repeatedly observed in acute myeloid leukemia (AML). However, the clinical impact of EWSR1 expression is still unclear in AML. Therefore, we explored the prognostic significance of EWSR1 in AML.

Methods: Bone marrow samples from 150 AML patients and 29 normal controls were collected, and qRT-PCR detected EWSR1 expression. The correlation between EWSR1 expression and clinical data in non-acute promyelocytic leukemia (non-APL) AML patients was analysed. A model was constructed for predicting 1-year, 2-year, and 3-year overall survival (OS). The molecular mechanisms of EWSR1 in AML were preliminarily explored through bioinformatics analysis.

Results: EWSR1 expression was upregulated in AML compared with normal controls (P = 0.009). High EWSR1 expression was associated with the European Leukemia Net (2022-ELN) adverse-risk non-APL AML (P = 0.006). Patients with high EWSR1 expression had shorter OS (294 days VS 812 days, P< 0.001) and shorter event free survival (EFS) (197 days VS 660 days, P = 0.001). Multivariate Cox regression analysis showed that high EWSR1 expression was an independent adverse prognostic factor for OS and EFS (P<0.05). The receiver operating characteristic curve, calibration curve and decision curve analysis showed that the model had better discrimination power for predicting 1-year, 2-year, and 3-year OS. The bioinformatics analysis suggested that EWSR1 may be involved in the progression of AML by regulating the cell cycle, senescence, apoptosis, PD-1 checkpoint pathway, and immune cell infiltration.

Conclusions: EWSR1 could be a powerful prognostic indicator for clinical strategy selection in AML. The prediction model may effectively predict the OS of non-APL AML.

Background: Acute myeloid leukemia (AML) is a genetic disorder caused by translocations or mutations that disrupt hematopoietic function and lead to malignant transformation. In recent years, microRNA-99a and miR-100 have been found to exhibit abnormal expression in solid tumors, but their roles in AML remain unclear. This study aims to investigate the expression levels of these two microRNAs in AML and their prognostic significance.

Methods: We analyzed bone marrow samples from 156 newly diagnosed adult AML patients at Jiangsu Institute of Hematology (JIH) using miRNA microarray analysis. Results were validated via RT-qPCR in a non-overlapping cohort of 87 AML patients and 10 healthy controls.

Results: miR-99a and miR-100 expression was significantly elevated in AML compared to controls. Expression of miR-99a and miR-100 was significantly decreased in CBF-AML (core binding factor acute myeloid leukemia) patients compared to non-CBF-AML patients. In AML patients, c-KIT mutational status was associated with the downregulated expression of miR-100. Moreover, low expression of miR-99a and miR-100 is associated with lower white blood cell (WBC) counts. Increased miR-100 levels in CBF-AML (with the t(8;21) subtype included) were associated with poor overall survival (OS); notably, within CBF-AML, the t(8;21) subtype AML patients showed the same trend, where higher miR-99a and miR-100 expression correlated with adverse OS.

Conclusion: These findings suggest that regulated expression of miR-99a and miR-100 is common in AML and that their expression correlates with prognosis in CBF-AML.

Purpose: We report the case of a 6-year-old boy who presented with muscular hypertonia, impaired growth, and recurrent infections, who was diagnosed with purine nucleoside phosphorylase (PNP) deficiency with two novel mutations in the PNP gene. He underwent a hematopoietic stem cell transplantation (HSCT) from an unrelated donor, and we observed the clinical outcome.

Methods: We retrospectively analyzed the clinical manifestations and outcomes of this patient who underwent HSCT. We analyzed the results of whole exome sequencing (WES) on the patient.

Results: The patient experienced repeated serious respiratory and gastrointestinal infections since birth and presented with neurological symptoms. He was found to have two novel pathogenic mutations in the PNP gene through WES. One hemizygous variant was c.385dup (p.Ile129Asnfs*6) in exon 4. The other was a heterozygous deletion in exon 2-6. He underwent HSCT with clinical improvement.

Conclusions: We presented a patient with two novel mutations in the PNP gene and clinical improvement following an allo-HSCT.

The tumor microenvironment (TME) represents a heterogeneous, complicated ecosystem characterized by intricate interactions between tumor cells and immune cells. During the past decade, immune cells especially T cells were found to play an important role in the progression of tumor and many related immune checkpoints drugs were created. In recent years, more and more scientists revealed the critical role of B-cells within the TME, particularly various populations of non-malignant B cells. Some studies indicated that non-malignant B cells may exert a 'double-edged sword' role in solid tumors. However, there has been comparatively less focus on the role of non-malignant B cells in hematologic malignancies. In this review, we characterized the development of B cells and summarized its functions of antitumor immunity within TME, with an emphasis on elucidating the roles and potential mechanisms of non-malignant B cells in the progression of hematologic diseases including classical Hodgkin's lymphoma, non-Hodgkin's B-cell lymphoma, non-Hodgkin's T-cell lymphoma, leukemia and multiple myeloma.