Exosome-based MRD detection in acute leukemias

Leukemia is a heterogeneous blood cancer characterized by multiple genetic and epigenetic aberrations resulting inthe uncontrolled growth of immature myeloid or lymphoid cells. Despite the advances in leukemia therapy, the disease relapse is responsible for the vast majority of death cases among leukemic patients. Measurable residual disease(MRD) is considered as a gold standard clinical practice for the therapy decision-making process to achieve long-lasting remission based on the detection and quantification of pre-and post-therapy-remaining leukemic blasts. However, relapse among negative MRD patients has been frequently reported highlighting the importance of other sensitive alternatives to detect MRD below the sensitivity of the existing MRD-detecting assays. Exosomes have emerged as a novel non-invasive approach of liquid biopsy to diagnose and monitor patients allowing to bypass limitations posed by other conventional methods. These nano-scale particles feature selective markers inherited fromtheir parental leukemic cells. The ability to immunophenotype leukemic cell-derived exosomes using multiparametric flow cytometry addresses an important question of whether they can be used for sensitive MRD detection. Therefore, translating this new diagnostic tool into clinical practice not only would revolutionize the detection of MRD in leukemic patients but also would offer a simple non-invasive method for sampling patients with hematological malignancies.