Background: Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is a severe medical emergency associated with high mortality rates and poor prognosis. Prompt and urgent treatment is crucial to address this medical emergency. This study aims to elucidate appropriate diagnostic thresholds for HL and investigate underlying mechanisms and potential targeted therapies.Methods: X-tile software was employed to analyze white blood cell (WBC) count thresholds in AML patients using data from TCGA and TARGET AML databases. METASCAPE and Gene Set Enrichment Analysis (GSEA) were conducted to explore the molecular mechanisms underlying HL in AML. Potential molecular targeted drugs were identified using the CELLMINER platform.Results: Analysis revealed that a WBC count threshold of 75×10⁹/L, rather than the conventional 100×10⁹/L, is more appropriate for diagnosing HL in adult AML patients. This revised threshold could aid clinicians in identifying a greater number of patients requiring immediate intervention. Significant correlations were observed between HL and specific mutations, including NPM1, FLT3, and DNMT3A. For pediatric AML patients, the HL threshold was determined to be 165×10⁹/L. Achieving complete remission (CR) or deeper levels of remission significantly reduces the risks associated with HL. The reduction in risk can lead to survival outcomes for HL patients that are comparable to those of non-hyperleukocytosis patients. Differential gene expression analysis indicated that downregulation of cell adhesion molecules is implicated in HL pathogenesis. Potential targeted therapies for AML with HL include Bcl2 inhibitors and histone deacetylase inhibitors. Clinical observations demonstrated that the addition of Bcl2 inhibitors, such as Venetoclax, to standard therapy results in a rapid reduction in WBC counts, thereby reducing tumor burden and providing prompt symptom relief. Combining these targeted drugs with conventional therapies appears promising in mitigating risks associated with HL.Conclusions: Lower diagnostic thresholds for HL in AML, identifies critical genetic correlations, and highlights effective molecular targeted therapies. Proactive early treatment is crucial for achieving deep remission and reducing HL risk. Future therapeutic strategies should consider integrating molecular targeted drugs with conventional therapies to improve outcomes for patients facing this high-risk hematological emergency.

Primary myelofibrosis (PMF) is characterized by bone marrow fibrosis, but the underlying molecular mechanisms remain incompletely understood. Here, we investigated the role of lysyl oxidase-like 2 (LOXL2), an enzyme involved in extracellular matrix remodeling, in PMF pathogenesis. Analysis of bone marrow cells from PMF patients revealed significantly elevated LOXL2 mRNA expression compared to healthy controls, which was further validated using 2 independent Gene Expression Omnibus datasets (GSE26049 and GSE12234). Serum LOXL2 protein levels were markedly increased in PMF patients (n = 38) compared to controls (n = 15) (P < .01), accompanied by significantly enhanced enzymatic activity (P < .05). Clinical analysis demonstrated that high LOXL2 enzyme activity correlated with adverse clinical features, including higher risk scores in both International Prognostic Scoring System (P = .029) and Dynamic International Prognostic Scoring System (P = .012) systems, and increased peripheral blood blast percentages (≥1%, P = .019). Notably, elevated LOXL2 enzyme activity emerged as an independent adverse prognostic factor in multivariate analysis. Gene set enrichment analysis revealed LOXL2’s association with multiple biological processes, including extracellular matrix remodeling, inflammatory responses, and JAK-STAT signaling pathways. Using CellMiner drug prediction analysis, we identified several FDA-approved drugs, particularly kinase inhibitors, as potential LOXL2-targeting therapeutics. Our findings demonstrate LOXL2’s critical role in PMF pathogenesis and suggest its potential as both a prognostic marker and therapeutic target in PMF treatment.

Objective: To analyze the etiological characteristics, antimicrobial resistance patterns of infections during the neutropenic phase in acute leukemia (AL) patients, and to evaluate the diagnostic value of soluble tumor necrosis factor receptor 1 (sTNF-R1) and interleukin-8 (IL-8). Methods: Clinical data from 142 AL patients in the neutropenic phase, admitted between July 2023 and July 2025, were retrospectively analyzed. Patients were divided into an infected group (n=63) and a non-infected group (n=79) according to the presence of hospital-acquired infections. Pathogen distribution and antimicrobial resistance were assessed in the infected group. Peripheral blood sTNF-R1 and IL-8 levels were measured within 24 hours after confirmed neutropenia and before antimicrobial therapy. Their diagnostic performance for concurrent infections was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Hospital-acquired infections occurred in 63 patients (44.37%), with bloodstream infections (39.68%) and respiratory tract infections being the most frequent. A total of 71 non-duplicate bacterial strains were isolated, of which 45 (63.38%) were Gram-negative, predominantly Escherichia coli (14 strains, 19.72%), and 26 (36.62%) were Gram-positive, predominantly Staphylococcus aureus (10 strains, 14.08%). High resistance rates were observed to multiple antimicrobials, particularly ampicillin among Gram-negative bacteria and penicillin among Gram-positive bacteria. Compared with the non-infected group, the infected group had higher white blood cell counts, lower albumin levels, and a greater proportion of unfavorable cytogenetic prognosis (all P < 0.05). sTNF-R1 and IL-8 levels were significantly higher in the infected group (both P < 0.001). These biomarkers showed significant negative correlations with neutrophil and albumin levels, and positive correlations with white blood cell count (all P < 0.05). The areas under the ROC curve (AUC) were 0.903 for sTNF-R1 and 0.910 for IL-8 individually, increasing to 0.932 when combined (P < 0.001). Conclusion: Infections during the neutropenic phase in AL patients are predominantly caused by Gram-negative bacteria and exhibit substantial antimicrobial resistance. Elevated sTNF-R1 and IL-8 levels are associated with infection in this population. Combined detection of these biomarkers demonstrates good diagnostic performance and may serve as a useful tool for early screening of infections.

Lung squamous cell carcinoma (LUSC) is a major challenge in oncology due to its high recurrence rate, highlighting the need to identify recurrence drivers. Based on the data provided by Zhang Zemin’s team in their research, we selected survival metadata from 119 patients with lung squamous cell carcinoma and data on the proportions of 51 immune cell types. We then combined machine learning methods to analyze the intrinsic tumor factors and tumor microenvironment (TME) in the recurrence of lung squamous cell carcinoma (LUSC). Chi-square tests identified immune cell subsets enriched in recurrent patients, such as high-MKI67 Tregs, low-FGFBP2 NK cells, low-FOXP3 Tregs, and low-KLRB1 CD8 + T cells. A random forest algorithm further pinpointed pathological response rate (PRR) as the primary predictive factor, with high-MKI67 Tregs as a key secondary contributor. Univariate and multivariate Cox regression analyses and Kaplan-Meier survival curves confirmed that pathological complete response (pCR) and low Treg_MKI67 expression were associated with better survival ( p = 0.0055 and p = 0.011, respectively). Patients achieving pCR and with low Treg_MKI67 expression had superior recurrence-free survival (RFS; 2-year RFS: 96.7% vs. 57.9% for non-pCR and high Treg_MKI67, p = 0.00066). These findings underscore the prognostic value of PRR and TME markers. They also highlight the potential of using single-cell RNA sequencing and machine learning to guide personalized therapies and reduce recurrence risk by targeting Treg activity, laying the groundwork for integrating immune markers into clinical practice to improve LUSC prognosis.

Objective: To investigate the relationship between the degree and duration of immunoparesis at diagnosis and poor prognosis in patients with newly diagnosed multiple myeloma (NDMM). Methods: A retrospective analysis was conducted on the clinical data of 258 patients with NDMM, including the status and duration of immunoparesis and the influence of other factors on prognosis. Results: 91.5% of NDMM had varying degrees of immunoparesis. The median progression-free survival (PFS) was significantly shorter in the severe immunoparesis group than in the non-severe immunoparesis group (25 months vs. 34 months, P = 0.0149). The median PFS was significantly shorter in the groups with severe immunoparesis lasting ≥ 3, ≥ 6, and ≥ 12 months than in the group with non-severe immunoparesis lasting (P ≤0.05). Osteolytic lesions, 17p deletion/mutation, hemoglobin < 85g/L, and severe immunoparesis lasting ≥ 12 months were independent poor prognostic factors for PFS (all P < 0.05). Circulating plasma cells ≥ 2% and osteolytic lesions were independent poor prognostic factors for overall survival (OS) (all P < 0.05). Conclusion: Immunoparesis at diagnosis and its duration are poor prognostic factors for PFS in patients with NDMM.

Lymphocyte-depleted classical Hodgkin lymphoma (LD-cHL) is a rare histologic subtype of classical Hodgkin lymphoma. This population-based study aimed to describe the clinical characteristics and prognostic factors of LD-cHL using data from the SEER registry.LD-cHL patients were older (median age 55 years, IQR: 37–72) than those with other subtypes (median age 38 years, IQR: 25–58; p < 0.001). They were more likely to present with advanced disease (35% Stage IV [N = 159] vs. 15% [N = 6,136]; p < 0.001). B symptoms were also more frequent in LD-cHL (67.8%, N = 307 vs. 54.5%, N = 23,025; p < 0.001).The 5-year overall survival rate for LD-cHL was 51.2% (95% CI: 46.7–56.2), lower than the 81.1% (95% CI: 80.7–81.5) observed in other subtypes. Random survival forest analysis identified age (variable importance: 0.31) and chemotherapy receipt (0.10) as the variables with the highest importance scores. Age stratification showed 5-year overall survival rates of 78.5% (95% CI: 72.5–85.1) for patients < 40 years, 43.3% (95% CI: 36.4–51.6) for those aged 40–60 years, and 15.6% (95% CI: 9.6–25.2) for those > 60 years. Chemotherapy receipt was associated with higher survival rates across all age groups.In subgroup analyses limited to patients who received chemotherapy, LD-cHL remained associated with inferior survival compared with other subtypes. Lymphoma-specific survival analysis yielded 5-year rates of 88.9%, 84.3%, and 60.5% in the < 40, 40–60, and > 60 years groups, respectively.This study confirms that LD-cHL is associated with older age, advanced stage at presentation, and relatively poor survival in real-world settings. Further studies with central pathological review and more detailed clinical data are needed to improve the understanding and management of this rare subtype.