Abstract Background: Extracellular vesicles (EVs) are biologically active nanoparticles. EVs from explant prostate cancer induce a neoplastic phenotype in normal prostate cell lines. We have also shown EVs from mesenchymal stem cells (MSC) can have a healing effect, reversing the malignant phenotype in prostate and colorectal cancer; as well as mitigating radiation damage to marrow. The role of EVs in leukemia and its microenvironment remains to be studied, and may provide insight for therapeutic advances. We hypothesize that EVs derived from normal MSC can have a healing effect, inhibiting the growth of myelogenous leukemia. Methods: Kasumi AML cells lines were seeded in a 96 well plate with various concentrations of MSC-derived EVs. Vesicles were isolated usingan established differential centrifugation technique, and were co-cultured with Kasumi. To study cellular proliferation we measured fluorescence after 60 min. Fluorescence intensities were normalized to control wells containing non-EV treated cells alone. Results: Proliferation of AML cells after one day of co-culture with MSC-EVs respectively was inhibited in a dose dependent manner. Three days of co-culture with similar doses resulted in ~40% and ~80%reduction in proliferation when normalized to control. At day 6 of co-culture growth was inhibited by ~80% at both EV concentrations when normalized to control. Summary/Conclusion: MSC-derived EVs inhibits the growth of the AMLcell line in vitro. This effect is seen as early as 1 day of co-culture andpersists out to 3, and 6 days implicating an miRNA-mediated mechanismthat has been discussed in previous works. We feel this is perhaps a modelof how a normal marrow works to suppress early cancer.As leukemia develops the cross-talk between AML and its microenvironmentalters the MSCs to promote a survival signal favouring AMLgrowth. Future work involves the capacity of AML-derived EVs to alterthe phenotype of normal marrow towards a pro-leuekmic phenotype.Employing mathematical models to quantify and ultimately predict thesechanges allows for precise therapeutic intervention. Citation Format: Theo Borgovan. A new biomarker in hematological malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1016.