Plasma Exosomes as Markers of Therapeutic Response in Patients with Acute Myeloid Leukemia

Purpose: Exosomes isolated from the plasma of newly-diagnosed acute myeloid leukemia (AML) patients have elevated protein and TGF-β1 contents and inhibit natural killer (NK) cell cytotoxicity. A potential role of exosomes in predicting responses to chemotherapy (CT) was evaluated in AML patients undergoing treatment. Experimental Design: Plasma was obtained from AML patients at diagnosis (n=16); post induction CT (n=9); during consolidation CT (n=10); in long-term remission (LTCR, n=5); and from healthy volunteers (n=7). Exosomes were isolated by exclusion chromatography and ultracentrifugation. The exosomal protein, soluble TGFβ-1 levels (ELISA) and the TGF-β1 profiles (western blots) were compared among patients’ cohorts. The results were correlated with the patients’ cytogenetic profile, percentage of leukemic blast and outcome. Results: At diagnosis, protein and TGF-β1 levels were higher (pConclusions: Changes in exosomal protein and/or TGF-β1 content may reflect responses to CT. The exosomal TGF-β1 profile suggests the presence of residual disease in patients considered to have achieved complete remission.