Chronic myeloid leukemia (CML) is a malignant hematologic disorder caused by abnormal proliferation of hematopoietic stem cells. In recent years, while the application of tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis of CML patients through in-depth exploration of pathogenesis of CML and advancements in targeted therapies, some patients still face challenges including drug resistance, disease relapse, and failure to achieve treatment-free remission. Imunotherapy, as a complementary or alternative strategy, holds significant potential for overcoming these limitations, and has gradually emerged as a critical research focus in CML treatment. This review aims to summarize the current research status and latest advances in immunotherapy for CML.

Objective: To develop a rapid quantification method for neutrophil extracellular traps (NETs) by quantifying neutrophils forming NETs (NETotic cells) on routine peripheral blood smears, and to evaluate the performance of an early warning model combining NETs with traditional coagulation indicators for risk of sepsis-induced coagulopathy (SIC) in septic patients. Methods: This prospective observational study was conducted in Wuxi People's Hospital Affiliated with Nanjing Medical University between May 2023 and May 2025. A total of 147 patients with sepsis (diagnosed based on Sepsis-3.0 criteria) who had not developed SIC [the international society on thrombosis and haemostasis (ISTH SIC score <4)] were enrolled. Blood samples were collected within 2 hours of admission. Neutrophil smudge cells (NETs%) were counted using an automated cell morphology analyzer. Serum levels of myeloperoxidase-DNA (MPO-DNA) complexes, circulating free DNA (cf-DNA) and sequential organ failure assessment (SOFA) scores were also determined. Based on progression to SIC (ISTH score ≥4) within 72 hours of admission, patients were categorized into a sepsis without SIC group (n=85) and a sepsis with SIC group (n=62). Risk factors were analyzed using binary logistic regression, receiver operating characteristic (ROC) curves were plotted, and the predictive value of NETs%, SOFA, and AT-Ⅲ for coagulation dysfunction was assessed. Results: The NETs% level was significantly higher in the sepsis with SIC group [8.50% (7.00, 11.50)] compared to both the healthy control group [1.00% (0.00, 2.00)] and sepsis without SIC group [4.40%(3.50, 6.50)] (P<0.01). NETs% was identified as an independent risk factor for SIC in sepsis patients. ROC analysis showed that the area under the curve (AUC) for predicting SIC was 0.90 for NETs%, 0.85 for MPO-DNA, and 0.79 for cf-DNA. The combined model of NETs% and SOFA score demonstrated the best performance, with an optimal cut-off value of 0.33, an AUC of 0.92, a sensitivity of 77%, and a specificity of 93%. Conclusion: NETs% shows promise as a novel biomarker for SIC. Peripheral blood smear morphology provides a simple, rapid, and cost-effective method for quantifying NETs%. NETs% enhances the early clinical identification of patients at high risk for SIC, and its combination with the SOFA score facilitates SIC prediction, offering a critical time window for initiating timely preventive interventions.

OBJECTIVE: To explore the clinical features, lysosomal enzymatic [acid α-glucosidase (GAA)] activities and genetic variants in a child with late-onset Pompe disease (LOPD). METHODS: Clinical data of a child who had presented at the Genetic Counseling Clinic of West China Second University Hospital in August 2020 was retrospectively analyzed. Blood samples were collected from the patient and her parents for the isolation of leukocytes and lymphocytes as well as DNA extraction. The activity of lysosomal enzyme GAA in leukocytes and lymphocytes was analyzed with or without addition of inhibitor of GAA isozyme. Potential variants in genes associated with neuromuscular disorders were analyzed, in addition with conservation of the variant sites and protein structure. The remaining samples from 20 individuals undergoing peripheral blood lymphocyte chromosomal karyotyping were mixed and used as the normal reference for the enzymatic activities. RESULTS: The child, a 9-year-old female, had featured delayed language and motor development from 2 years and 11 months. Physical examination revealed unstable walking, difficulty in going upstairs and obvious scoliosis. Her serum creatine kinase was significantly increased, along with abnormal electromyography, whilst no abnormality was found by cardiac ultrasound. Genetic testing revealed that she has harbored compound heterozygous variants of the GAA gene, namely c.1996dupG (p.A666Gfs*71) (maternal) and c.701C>T (p.T234M) (paternal). Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1996dupG (p.A666Gfs*71) was rated as pathogenic (PVS1+PM2_Supporting+PM3), whilst the c.701C>T (p.T234M) was rated as likely pathogenic (PM1+PM2_Supporting+PM3+PM5+PP3). The GAA in the leukocytes from the patient, her father and mother were respectively 76.1%, 91.3% and 95.6% of the normal value without the inhibitor, and 70.8%, 112.9% and 128.2% of the normal value with the inhibitor, whilst the activity of GAA in their leukocytes had decreased by 6 ~ 9 times after adding the inhibitor. GAA in lymphocytes of the patient, her father and mother were 68.3%, 59.0% and 59.5% of the normal value without the inhibitor, and 41.0%, 89.5% and 57.7% of the normal value with the inhibitor, the activity of GAA in lymphocytes has decreased by 2 ~ 5 times after adding the inhibitor. CONCLUSION The child was diagnosed with LOPD due to the c.1996dupG and c.701C>T compound heterozygous variants of the GAA gene. The residual activity of GAA among LOPD patients can range widely and the changes may be atypical. The diagnosis of LOPD should not be based solely on the results of enzymatic activity but combined clinical manifestation, genetic testing and measurement of enzymatic activity.
Humans ; Child ; Male ; Female ; Glycogen Storage Disease Type II/pathology* ; Retrospective Studies ; alpha-Glucosidases/genetics* ; Mothers ; Lysosomes/pathology* ; Mutation