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Tyrosine kinase inhibitors (TKI) have emerged as a paradigm-shifting therapeutic approach for the treatment of chronic myeloid leukemia (CML) following their regulatory approval in 2001. These agents have revolutionized the management of CML by significantly improving patient outcomes and enabling them to achieve near-normal life expectancies. Consequently, the utilization of TKI has become increasingly prevalent, accompanied by the recognition and management of their associated adverse effects. Given the expanding patient population receiving TKI therapy, it is imperative that hematologists, as well as general practitioners, assume the responsibility of closely and meticulously monitoring patients' treatment progress while effectively addressing the occurrence of any untoward effects., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Targeting chemoresistant malignant cells is one of the current major challenges in oncology. Therefore, it is mandatory to refine the characteristics of these cells to monitor their survival and develop adapted therapies. This is of particular interest in acute myeloid leukemia (AML), for which the 5-year survival rate only reaches 30%, regardless of the prognosis. The role of the microenvironment is increasingly reported to be a key regulator for blast survival. In this context, we demonstrate that contact with mesenchymal stromal cells promotes a better survival of blasts in culture in the presence of anthracycline through the activation of ABC transporters. Stroma-dependent ABC transporter activation leads to the induction of a Side Population (SP) phenotype in a subpopulation of primary leukemia blasts through alpha (α)4 engagement. The stroma-promoting effect is reversible and is observed with stromal cells isolated from either healthy donors or leukemia patients. Blasts expressing an SP phenotype are mostly quiescent and are chemoresistant in vitro and in vivo in patient-derived xenograft mouse models. At the transcriptomic level, blasts from the SP are specifically enriched in the drug metabolism program. This detoxification signature engaged in contact with mesenchymal stromal cells represents promising ways to target stroma-induced chemoresistance of AML cells., (Copyright© 2020 Ferrata Storti Foundation.)