@article{Pelosi_Castelli_Testa_2022, title={THE GROWING ROLE OF THE BH3 MIMETIC DRUG VENETOCLAX IN THE THERAPY OF ACUTE MYELOID LEUKEMIA}, volume={14}, url={https://www.mjhid.org/mjhid/article/view/5150}, DOI={10.4084/MJHID.2022.080}, abstractNote={<p>In spite recent progresses, acute myeloid leukemia (AML) remains a disease associated with poor prognosis, particularly in older AML patients unfit to tolerate intensive chemotherapy treatment. The development and introduction in therapy of the drug Venetoclax, a potent BH3 mimetic targeting the antiaopoptotic protein BCL-2, inducing apoptosis of leukemic cells, has shown to be a promising treatment for newly diagnosed, relapsed and refractory AML patients ineligible for induction chemotherapy. Combination treatments using Ventoclax and a hypomethylating agent (azacytidine or decitabine) or low-intensity chemotherapy have shown in newly diagnosed patients variable response rates, with highly responsive patients with <em>NPM1, IDH1-IDH2, TET2 </em>and <em>RUNX1 </em>mutations and with scarcely responsive patients with <em>FLT3, TP53 </em>and <em>ASXL1 </em>mutations, complex karyotypes and secondary AMLs. Patients with refractory/relapsing disease are less responsive to Venetoclax-based regimens.</p> <p>However, in the majority of patients the responses have only a limited duration and development of resistance is frequently observed. Understanding mechanisms of resistance is of crucial importance for the development of new strategies and identification of rational drug combination regimens. In this context, two strategies seem to be promising: (i) triplet therapies based on the combined administration of Venetoclax, a hypomethylating agent (or low-dose chemotherapy) and an agent targeting a specific genetic alteration of leukemic cells (i.e., FLT3 inhibitors in <em>FLT3</em>-mutated AMLs) or an altered signaling pathway; (ii) combination therapies based on the administration of two BH3 mimetics (i.e., BCL-2 +MCL-1 mimetics) and a hypomethylating agent.</p>}, number={1}, journal={Mediterranean Journal of Hematology and Infectious Diseases}, author={Pelosi, Elvira and Castelli, Germana and Testa, Ugo}, year={2022}, month={Oct.}, pages={e2022080} }