Resistance mechanisms in therapy of acute myeloid leukemia

IN ENGLISH LANGUAGE Candidate: Mgr. Simona Suchá Supervisor: Assoc. Prof. PharmDr. Martina Čečková, PhD. Title of the doctoral thesis: Resistance mechanisms in therapy of acute myeloid leukemia Acute myeloid leukemia (AML) is a hematologic cancer known for its extensive heterogeneity, poor treatment outcomes and high relapse rate. Therapy outcome is often compromised by highly resistant leukemic clones present at diagnosis, which evade chemotherapy and continue to spread the disease. Identification of their cellular features is, therefore, a key in successful targeting and eliminating of these resistant leukemic cells. AML cells can, however, develop drug resistance even overtime due to prolonged drug exposure. Extremely high adaptability of leukemic cells enables them to survive whenever therapeutic stress stimuli occur. Uncovering molecular mechanisms that cells utilize to activate their survival mode is crucial in selection of treatment leading to maximal efficacy. Based on these grounds, two main aims of this thesis were set. First, to determine clinical relevance of ABC efflux transporters in AML and to evaluate the effect of targeted agents on chemotherapy. The focus was put on agents belonging to either FLT3 inhibitors (midostaurin) or CDK4/6 inhibitors (abemaciclib, palbociclib,..