Cardiometabolic diseases, including cardiovascular disorders and type 2 diabetes mellitus, are the leading cause of morbidity and mortality worldwide, placing a significant burden on healthcare systems. Although advances in imaging and risk stratification have improved disease management, conventional diagnostic and prognostic tools often lack the requisite sensitivity and specificity for early and precise risk stratification. This limitation stems from their poor ability to capture the full molecular complexity of these conditions, underscoring an urgent need for innovative biomarkers to bridge these gaps. MicroRNAs, small non-coding RNAs that regulate gene expression post-transcriptionally, have emerged as promising candidates. Their characteristics offer several advantages over traditional methods, including exceptional stability in biological fluids, strong tissue and disease specificity, and the ability to reflect dynamic pathological changes. These unique features enable miRNAs to detect subtle molecular alterations that may precede clinical symptoms, thereby overcoming key limitations of current diagnostic approaches. Altered circulating miRNA profiles have been linked to pathological processes such as endothelial dysfunction, inflammation, oxidative stress, and maladaptive cardiac remodeling. This review provides a comprehensive overview of the current evidence supporting the diagnostic and prognostic role of circulating miRNAs in cardiometabolic disease. We highlight their potential as early detection biomarkers, tools for patient stratification, and indicators of therapeutic response. Furthermore, we discuss key limitations to clinical translation, including methodological variability, challenges in sample handling, differences in normalization strategies, and platform-dependent quantification inconsistencies. Overcoming these obstacles and achieving robust large-scale clinical validation will be essential to fully harness the potential of miRNAs as next-generation molecular signatures in precision medicine.

Cardiometabolic and cardiovascular diseases (CVDs) remain the leading cause of death worldwide, with well-established risk factors such as smoking, obesity, and diabetes contributing to plaque formation and chronic inflammation. However, emerging evidence suggests that the immune system plays a more significant role in the development and progression of CVD than previously thought. Specifically, the finely tuned regulation of lymphocyte subsets governs post-injury inflammation and tissue damage resolution and orchestrates the functions and activation of endothelial cells, cardiomyocytes, and fibroblasts in CVD-associated lesions (e.g., atherosclerotic plaques). A deeper understanding of the immune system’s involvement in CVD development and progression will provide new insights into disease biology and uncover novel therapeutic targets aimed at re-establishing immune homeostasis. In this review, we summarize the current state of knowledge on the distribution and involvement of lymphocyte subsets in CVD, including atherosclerosis, diabetes, hypertension, myocardial infarction, and stroke.

Background/Objectives: Clonal evolution is mainly defined based on the appearance or expansion of clones harboring specific somatic mutations and/or cytogenetic abnormalities, whereas few studies have investigated immunophenotypic heterogeneity assessed by flow cytometry and its relationship with disease progression. In this study, flow cytometry immunophenotyping of acute myeloid leukemia (AML) was carried out to identify phenotypic subclones based on antigen expression and to investigate clonal sweep. Methods: A total of 24 patients diagnosed with AML followed at the Hematology and Transplant Center of Salerno were included. Bone marrow or peripheral blood specimens were subjected to flow cytometry immunophenotyping and leukemic cell characterization. Phenotypic profiles were also compared to molecular alterations detected by next-generation sequencing. Results: We found that flow cytometry-defined clonal heterogeneity was more complex than molecular heterogeneity at diagnosis and disease relapse. Flow cytometry enabled the identification of small phenotypic subclones that were not detected by molecular profiling and that, in several cases, expanded over time, consistent with a phenotypic clonal sweep. The presence of small clones was associated with shorter progression-free survival and overall survival. Conclusions: Flow cytometric clonal heterogeneity, especially the presence of small clones (defined by antigen expression from 2 to 30%), may serve as an additional prognostic factor in AML. Immunophenotyping integrated with molecular data may improve risk stratification, enhance measurable residual disease assessment, and contribute to a more personalized disease monitoring strategy.

Background/Objectives: Hematogones, B cell precursors, are considered a clock of bone marrow reconstitution after chemotherapy and hematopoietic stem cell transplantation (HSCT). Methods: In this retrospective observational monocentric study, we investigated the prognostic role of hematogone expansion after allogeneic HSCT and its association with clinical and molecular features. Results: Using a cut-off value of 0.1%, hematogones were detected in 60% of patients at the first re-evaluation after HSCT (median, 2.4%; range, 0.2–9.0%) and in 63% of subjects at the most recent evaluation (MRR) (median, 1.4%; range, 0.1–5.1%). In particular, prolonged hematogone expansion was associated with longer overall survival (p = 0.0043) and relapse-free survival (p = 0.0002). No associations were described between hematogone frequency and stem cell sources or acute or chronic graft versus host disease incidence. Conclusions: In conclusion, our results confirmed that hematogones mirrored bone marrow fitness and reconstitution ability; thus, they could be used as a prognostic marker of HSCT outcomes.