Clinical and Experimental Medicine最新文献

The chromosomal translocation t(11;14)(q13;q32) is frequently observed in systemic light-chain (AL) amyloidosis, yet its clinical significance in the era of daratumumab-based therapy remains unclear. To compare clinical and cytogenetic characteristics, we retrospectively analyzed 68 patients with systemic AL amyloidosis and 107 patients with multiple myeloma (MM) newly diagnosed at Kumamoto University Hospital, with the MM cohort serving as a reference cohort. t(11;14) was detected in 55.9% of AL amyloidosis and 28.0% of MM cases. In both diseases, t(11;14) was associated with light chain-only M-protein and elevated CD20 expression on bone marrow plasma cells, suggesting a distinct phenotype. Notably, t(11;14)-positive AL amyloidosis patients exhibited a significantly lower incidence of renal dysfunction, a feature not observed in t(11;14)-positive MM. Among 47 AL amyloidosis patients treated with upfront daratumumab-containing regimens, overall survival did not differ significantly by t(11;14) status. However, event-free survival was significantly shorter in the t(11;14)-positive group (median 41.6 vs. 71.3 months, p = 0.037), accompanied by inferior 3 months hematological and cardiac responses. These findings suggest that t(11;14)-positive AL amyloidosis constitutes a distinct biological and clinical subtype characterized by delayed treatment response to daratumumab. Tailored therapeutic strategies targeting the unique biology of t(11;14)-positive AL amyloidosis is warranted.

A single-center prospective study was conducted at a tertiary care hospital in Kuopio Finland over the past two decades, searching for novel biomarker candidates to predict complicated course of febrile neutropenia (FN) in hematological patients. In Dec 2006‒Dec 2015, 85 patients with acute myeloid leukemia and 179 autologous hematopoietic stem cell transplant recipients were included. More than 20 biomarkers were evaluated in subsequent patient cohorts and compared to C-reactive protein (CRP) and procalcitonin (PCT). The samples were taken on d0-d2 from the beginning of FN. Here, we provide an overview of the results of these studies. Most biomarkers evaluated did not provide additional prognostic benefit compared to CRP or PCT. The most promising biomarkers warranting further studies include soluble cluster of differentiation 14, interleukin-1-receptor antagonist, interleukin-10, tissue inhibitor of matrix metalloproteinase-1, and caspase-cleaved cytokeratin-18. Several biomarkers evaluated in this series of studies are hampered by impaired production by neutrophils/leukocytes (matrix metalloproteinase-8, cell-free plasma DNA and soluble urokinase plasminogen activator receptor) or platelets (vascular endothelial growth factor). For now, these novel biomarkers cannot substitute the conventional markers nor provide additional benefit in routine use. Optimally, the most promising novel markers should be evaluated in prospective multicenter studies with higher patient numbers and several endpoints to more reliably evaluate their performance. At present, close patient monitoring is imperative in hematological patients with FN. The additional information provided by novel FN biomarkers may be useful, but they should be evaluated combined with daily evaluation of sepsis scoring systems.

Patients with hyperthyroidism frequently present with hematological abnormalities; however, the underlying mechanisms remain incompletely understood. This study enrolled 166 treatment-naïve hyperthyroidism patients and 56 age- and sex-matched healthy controls, comparing their complete blood count parameters. Additionally, a murine model of hyperthyroidism was established, and flow cytometry was employed to assess the quantity, proportion, cell cycle status, and apoptosis of hematopoietic stem/progenitor cells (HSPCs) in the bone marrow. Clinical data analysis revealed that, compared to the healthy control group, hyperthyroidism patients exhibited significant reductions in peripheral white blood cell counts-particularly neutrophils, eosinophils, and basophils-as well as in red blood cell parameters, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (HCH), and mean corpuscular hemoglobin concentration (MCHC). These alterations were more pronounced in female patients. Animal experiments confirmed that hyperthyroid mice also developed leukopenia and neutropenia. Further investigation demonstrated a decreased number of HSPCs in the bone marrow of hyperthyroid mice. The primary cause was identified as cell cycle arrest rather than increased apoptosis. This study reveals that elevated thyroid hormone levels may lead to alterations in peripheral blood cell counts by inducing cell cycle arrest in bone marrow HSPCs, thereby impairing their proliferation and differentiation capabilities. These findings provide a novel cellular perspective for understanding the mechanisms underlying hematological abnormalities in hyperthyroidism and offer a theoretical foundation for potential clinical intervention strategies.

Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy where traditional DNA sequence-based classification fails to fully explain clinical outcomes. This review explores the dynamic and multifaceted role of the epigenome as a critical driver of leukemogenesis, progression, and therapeutic resistance. We detail how disruptions in DNA methylation, histone modifications, chromatin architecture, and non-coding RNAs create a complex regulatory landscape that transcends genetic alterations. We highlight the emergence of single-cell multi-omics technologies, which are resolving intratumoral heterogeneity and uncovering the epigenetic signatures of leukemic stem cells. Furthermore, we discuss the significant translational potential of these discoveries, including the development of epigenetic biomarkers for refined risk stratification, minimal residual disease (MRD) monitoring, and predicting response to novel epigenetic therapies like menin and LSD1 inhibitors. Integrating these dynamic epigenetic layers into clinical decision-making promises to usher in a new era of precision medicine, ultimately improving prognostic accuracy and therapeutic outcomes for AML patients.

At present, the role of Cysteine and glycine rich protein 1 (CSRP1) in the occurrence and development of diffuse large B lymphoma (DLBCL) has not been reported. We conducted a comprehensive analysis of the potential value of CSRP1 in DLBCL using multiple independent datasets and analytical methods, including differential expression analysis, pathway analysis and immune analysis. Then, cell experiments were used to confirm the regulatory role of CSRP1 in DLBCL. The analysis results show that in DLBCL patients, the expression of CSRP1 is significantly upregulated. In addition, CSRP1 is associated with the cell cycle related pathways and immune microenvironment in DLBCL. Cell experiments confirmed that CSRP1 can significantly regulate the apoptosis and cycle progression of DLBCL cells. In conclusion, CSRP1 may be a potential therapeutic target for DLBCL patients, our research provides a theoretical basis for improving the clinical treatment of DLBCL.