Background: Acute myeloid leukemia (AML), as the most common subtype of leukemia in adults, is characterised by rapid progression and poor prognosis. In the context of the rapid development of medical technology and the complexity of social factors, a detailed report describing the latest epidemiological patterns of AML is important for decision makers to allocate healthcare resources effectively. Methods: Our research utilized the latest data sourced from the Global Burden of Disease (GBD) 2021. To delineate the burden of AML, we comprehensively described the incidence, deaths, disability-adjusted life years (DALYs), and the associated age-standardized rates per 100,000 persons (ASR) spanning from 1990 to 2021 stratifies according to age, sex, socio-demographic index (SDI), and nationality. Additionally, we extracted and analyzed data about the risk factors that contribute to AML-related deaths and DALYs. Results: According to our study, the incidence of AML has continued to rise globally from 79,372 in 1990 to 144,645 in 2021 and AML affected the male and the elderly populations disproportionately. Furthermore, there was a significant positive correlation between the burden of AML and the SDI value. Developed nations generally exhibited higher age-standardized incidence rate, age-standardized death rate, and age-standardized disability-adjusted life year rate than the developing nations. We also analyzed the prevalence of smoking, high body mass index, and occupational benzene and formaldehyde exposure in the AML population in different SDI regions. Moreover, smoking and high body mass index were more prevalent in developed countries, whereas occupational exposure to these chemicals was the predominant risk factor in developing countries. Conclusion: The global burden of AML has increased over the past 32 years, with rising morbidity and mortality. The incidence of AML is differentially distributed across different SDI countries or regions. AML incidence is higher in the elderly and in men. The proportions of smoking, high body mass index, and occupational exposure to benzene and formaldehyde varied by region. The findings highlight the need for region-specific prevention and call for future research on preventive strategies and new treatments to lower AML incidence and improve patient outcomes.

Background: Outcomes of chronic myeloid leukemia (CML) has been improved dramatically in the past two decades, but survival levels of CML patients varied in regions. Comprehensive epidemiological research is necessary to evaluate the global burden of CML.Methods: All data used in our study came from the Global Burden of Disease (GBD) study 2017. Incidence cases, death cases, disability-adjusted life-years (DALYs), and its corresponding age-standardized rate between 1990 to 2017 were used to describe the distribution of CML burden, according to age, sex, social-demographic index (SDI), and countries. Data about attributable risk factors contributing to CML deaths and DALYs were also extracted and analyzed.Results: Globally, the disease burden of CML gradually decreased from 1990 to 2017. Higher SDI countries achieved a remarkable effect on diminishing the CML burden. Conversely, due to population growth, the incidence cases, death cases, and DALYs of CML in lower SDI quintiles showed an upward trend. India had the most incidence cases and death cases of CML in the world. Additionally, smoking was the most significant attributable risk factor contributing to CML deaths and DALYs, followed by high body mass index.Conclusion: The disease burden of CML decreased globally, especially in higher SDI countries in the past 28 years. The increasing incidence cases and death cases were mainly observed in lower SDI countries. Additionally, strategies to control modifiable risk factors such as smoking and high body mass index might be useful in diminishing mortality and DALYs.

Purpose: To investigate the efficacy and safety of the novel orally active PI3Kδ inhibitor in relapsed and/or refractory patients with follicular lymphoma (FL) who had received at least two prior systemic treatments. Patients and Methods: Histologically confirmed relapsed and/or refractory patients with FL with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate, and drug safety profile. Results: Of 114 screened relapsed and/or refractory patients with FL, 84 were enrolled in the full analysis set (FAS). The ORR of the 84 FAS patients was 79.8% [95% confidence interval (CI), 69.6–87.8, 67 patients], with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (95% CI, 9.3–15.9). The median PFS was 13.4 months (95% CI, 11.1–16.7). The 12-month OS rate was 91.4% (95% CI, 82.7–95.8) and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events Grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%), and interstitial lung disease (3.6%). Conclusions: Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory patients with FL who had received at least two prior systemic therapies.

DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mutated acute myeloid leukemia (AML) has a poor prognosis, but the exact mechanism is still unclear. Here, we aimed to explore the mechanism of immune escape in AML with DNMT3A mutation. We constructed a DNMT3A knockout clone and DNMT3A-R882H-mutated clones. RNA-seq results showed that transcription factors and macrophage inflammatory proteins were significantly downregulated in the DNMT3A mutant clones. KEGG enrichment and gene set enrichment analysis (GSEA) showed that a large number of genes were enriched in inflammatory immune-related pathways, such as the toll-like receptor signaling pathway. Therefore, we co-cultured AML cells with macrophages. The DNMT3A-mutated AML cells attenuated M1 macrophage polarization and resisted its killing effect in vitro and in vivo. In xenografts, the tumor volumes in the experimental group were significantly larger than those in the control group, and the proportion of M2 macrophages was significantly higher. After the co-culture, the increase in pro-inflammatory cytokine expression in the mutant cells was significantly lower than that in the control group, while that in immunosuppressive factors was not significantly different. In co-cultivated supernatants, the concentration of inflammatory factors in the experimental group was significantly lower than that in the control group, while that of immunosuppressive factors was significantly higher. Resistin significantly promoted the expression of inflammatory proteins in AML cells. It relieved the inhibitory effect of DNMT3A mutation, promoted the phenotypic recovery of the co-cultured macrophages, eliminated resistance, and regulated the immune microenvironment. Thus, resistin may serve as an ancillary drug for patients with DNMT3A-mutated AML.

Abnormalities in haemostasis are often detected in patients with multiple myeloma and the fundamental factors that lead to these abnormities are worthy of exploration. The objective of this study was to investigate bleeding diathesis and coagulopathy in different multiple myeloma types or stages and assess how paraprotein concentration contributes to differences in these conditions. Haemostasis screening tests and serum monoclonal protein (M protein) concentration were retrospectively analysed in 101 patients newly diagnosed with multiple myeloma from January 2012 to April 2014. No significant differences were found between bleeding diathesis and types or International Staging System (ISS) stages of multiple myeloma; however, prolonged thrombin time (TT) was found in most of patients (77.7%) and was positively related to light-chain concentration (P ≤ 0.01). Prolonged prothrombin time (PT) was more obvious in IgA and IgG-type multiple myeloma than in the light-chain type (P ≤ 0.01). With increased clinical staging, PT remarkably increased (P ≤ 0.01). M protein concentration was significantly higher in patients with prolonged PT than in those with normal PT (P ≤ 0.01). The D-dimer mean was significantly higher than normal (>0.5 μg/ml) (P ≤ 0.01). Fibrinogen was negatively related to M protein levels (P ≤ 0.01); however, there was no correlation between activated partial thromboplastin time (APTT) and multiple myeloma stages or types, M protein levels and serum light-chain concentration (P ≥ 0.05). Patients with light-chain type multiple myeloma were more likely to have prolonged TT than patients with other types. M protein levels had an obvious effect on PT. Prolonged PT was more common in IgA and IgG-type multiple myeloma. Abnormal haemostasis test results are not always accompanied by clinically apparent haemostatic complications.

Acute myeloid leukemia (AML) is the most prevalent form of leukemia among adults, characterized by aggressive behavior and significant genetic diversity. Despite decades of reliance on conventional chemotherapy as the mainstay treatment, patients often struggle with achieving remission, experience rapid relapses, and have limited survival prospects. While intensified induction chemotherapy and allogeneic stem cell transplantation have enhanced patient outcomes, these benefits are largely confined to younger AML patients capable of tolerating intensive treatments. DNMT3A, a crucial enzyme responsible for establishing de novo DNA methylation, plays a pivotal role in maintaining the delicate balance between hematopoietic stem cell differentiation and self-renewal, thereby influencing gene expression programs through epigenetic regulation. DNMT3A mutations are the most frequently observed genetic abnormalities in AML, predominantly in older patients, occurring in approximately 20–30% of adult AML cases and over 30% of AML with a normal karyotype. Consequently, the molecular underpinnings and potential therapeutic targets of DNMT3A mutations in AML are currently being thoroughly investigated. This article provides a comprehensive summary and the latest insights into the structure and function of DNMT3A, examines the impact of DNMT3A mutations on the progression and prognosis of AML, and explores potential therapeutic approaches for AML patients harboring DNMT3A mutations.