The small extracellular vesicles (sEV) accumulating in acute myeloid leukemia (AML) patients\' plasma are mixtures of vesicles produced by leukemic and non-malignant cells. sEV originating from leukemia blasts could serve as potential non-invasive biomarkers of AML response to therapy. To isolate blast-derived sEV from patients\' plasma, we developed a bioprinted microarray-based immunoassay using monoclonal antibodies (mAbs) specific for leukemia-associated antigens (LAAs) and mAbs specific for a mix of tetraspanins (CD9, CD63, and CD81). We determined the proportion of LAA+ sEV relative to total plasma sEV (the LAA+/total sEV ratio) in serially collected samples of newly diagnosed AML patients prior to, during, and after chemotherapy. At AML diagnosis, the LAA+/total sEV ratio was significantly higher in patients than in healthy donors (HDs). In patients who achieved complete remission (CR) after induction chemotherapy, the LAA+/total sEV ratios significantly decreased after each chemotherapy cycle to levels seen in HDs. In contrast, the LAA+/total sEV ratios in AML patients with persistent leukemia after therapy remained elevated during and after therapy, as did the percentage of leukemic blasts in these patients\' bone marrows. The LAA+/total sEV ratio emerges as a promising non-invasive biomarker of leukemia response to therapy.

Despite decades of research, glioblastoma (GBM) remains invariably fatal among all forms of cancers. The high level of inter- and intratumoral heterogeneity along with its biological location, the brain, are major barriers against effective treatment. Molecular and single cell analysis identifies different molecular subtypes with varying prognosis, while multiple subtypes can reside in the same tumor. Cellular plasticity among different subtypes in response to therapies or during recurrence adds another hurdle in the treatment of GBM. This phenotypic shift is induced and sustained by activation of several pathways within the tumor itself, or microenvironmental factors. In this review, the dynamic nature of cellular shifts in GBM and how the tumor (immune) microenvironment shapes this process leading to therapeutic resistance, while highlighting emerging tools and approaches to study this dynamic double-edged sword are discussed.