Acute myeloid leukemia (AML) is a heterogeneous group of clonal myeloid disorders characterized by intrinsic molecular variability. Pretreatment cytogenetic and mutational profiles only partially inform prognosis in AML, whereas relapse is driven by residual leukemic clones and mere morphological evaluation is insensitive for relapse prediction. Measurable residual disease (MRD), an independent post-diagnostic prognosticator, has recently been introduced by the European Leukemia Net as a new outcome definition. However, MRD techniques are not yet standardized, thus precluding its use as a surrogate endpoint for survival in clinical trials and MRD-guided strategies in real-life clinical practice. AML resistance and relapse involve a complex interplay between clonal and immune cells, which facilitates the evasion of the leukemic clone and which is not taken into account when merely quantifying the residual leukemia. Multiparameter flow cytometry (MFC) offers the possibility of capturing an overall picture of the above interactions at the single cell level and can simultaneously assess the competence of anticancer immune response and the levels of residual clonal cells. In this review, we focus on the current status of MFC-based MRD in diverse AML treatment settings and introduce a novel perspective of combined immune and leukemia cell profiling for MRD assessment in AML.
The efficient and targeted delivery of pharmaceutical substances remains a major challenge in modern therapeutics. Traditional drug delivery systems often suffer from limited bioavailability, rapid clearance, and off-target effects. Red blood cells (erythrocytes), due to their long circulation time, biocompatibility, and immune-evasive properties, have emerged as promising carriers in the development of novel nanotechnology-based drug delivery platforms.A comprehensive literature review was conducted, analyzing recent studies on erythrocyte membrane-coated nanoparticles, their interactions with loaded therapeutic agents, and their performance in vitro and in vivo. Special focus was given to applications in chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and immunotherapy. Erythrocyte-based nanocarriers demonstrated improved circulation times, reduced immune clearance, and enhanced targeting capabilities compared to traditional nanoparticles. Encapsulation of nanoparticles within erythrocyte membranes preserved the functional integrity of the carrier while minimizing systemic toxicity. However, challenges such as membrane stability, hemocompatibility, and the potential for nanoparticle-induced hemoglobin dysfunction were identified as areas requiring further research. In conclusion, erythrocyte membrane-coated nanoparticles represent a unique and promising strategy for drug delivery, combining the natural advantages of red blood cells with the versatility of nanotechnology.
4 September 2023 in European Journal of Haematology
Multiple myeloma (MM) is a well known hematological neoplasm, characterized by aberrant plasma cell proliferation, commonly producing increased numbers of monoclonal immunoglobulins, causing osteol...
Mature erythrocytes are traditionally regarded as anucleate cells lacking nuclear DNA. However, evidence shows they retain residual genetic material, including mitochondrial DNA (mtDNA) and RNA fragments. This review explores the role of such genetic material in cellular function, diagnostics, and erythropoiesis. A comprehensive literature review was conducted, focusing on (i) erythropoiesis, (ii) enucleation of erythroid precursors, (iii) the presence of DNA in red blood cells (RBCs), and (iv) RNA fragments such as messenger RNA (mRNA), microRNA (miRNA), and other non-coding RNAs. Mature RBCs harbor small amounts of DNA and diverse RNA species. Residual DNA can act as damage-associated molecular patterns (DAMPs), triggering immune responses when released under stress or injury. RNA fragments reflect the transcriptional activity of precursor cells and have been linked to potential diagnostic applications. Studies suggest that RBC-derived RNA signatures may serve as non-invasive biomarkers for diseases such as diabetes, cardiovascular conditions, and hematological disorders. These profiles mirror changes in erythropoiesis and provide insights into systemic pathophysiology. Residual genetic material in RBCs extends their role beyond oxygen transport. It contributes to immune modulation and may provide novel diagnostic and therapeutic opportunities, enhancing disease detection and understanding of erythropoiesis.
Alzheimer’s disease (AD) remains a major neurodegenerative disorder lacking effective long-term disease-modifying therapies. Current pharmacological approaches provide primarily symptomatic benefit, while recently approved anti-amyloid monoclonal antibodies offer only modest clinical efficacy and are constrained by safety concerns, high costs, and limited blood–brain barrier (BBB) penetration. In this context, exosome-based strategies have emerged as potential therapeutic platforms in AD research. As endogenous nanovesicles, exosomes exhibit favorable biocompatibility, intrinsic BBB-crossing capacity, and the ability to deliver diverse therapeutic cargo across multiple pathological pathways. Through bioengineering approaches, exosomes may additionally be optimized for targeted brain delivery and therapeutic personalization. Nevertheless, despite their conceptual and preclinical advantages, exosome-based therapies remain at an early translational stage, with unresolved challenges related to large-scale production, standardization, biodistribution, and long-term safety. This review provides a comparative translational analysis of conventional and exosome-based therapeutic strategies in AD, focusing on mechanistic targeting, delivery efficiency, safety and tolerability, therapeutic personalization, and translational readiness. We critically evaluate the extent to which exosome-based platforms may address the limitations of current therapies while highlighting the key barriers that continue to limit their clinical translation and real-world applicability.