Leukemia treatment: studies exploring bone marrow microenvironment, drug resistance and cannabidiol

The results described in this thesis highlight the role of human regenerative associated endothelial cells (hRECs) in the bone marrow microenvironment and hematopoiesis. By being resistant to 5-FU therapy, hRECs remain active in secreting factors enabling enhanced expansion of precursor HSC. A second part of this thesis provides novel insights into the role of specific influx and efflux transporters implicated in the efficacy/resistance of MTX and Ara-C. Finally, a third part described the results of in vitro experimental anti-leukemia therapeutics with cannabidiol, revealing double-edged effects: anti-leukemic effects at high doses of CBD and cell growth stimulatory effects at low doses of CBD. Together, these results may contribute to improve anti-leukemic chemotherapy efficacy and minimize toxicity.