Mechanisms of drug resistance in myelodysplastic syndromes and acute myeloid leukemia

Abstract

Resistance to chemotherapy remains the major obstacle to achieving durable, complete remissions in patients with myeloid malignancies. In many cases, patients respond to induction therapy, but the remission is of short duration and is associated with resistance to conventional antineoplastics at relapse. These resistant cells may be present at diagnosis or develop during treatment. In recent years, an important mechanism of pleiotropic drug resistance, multidrug resistance (MDR), as well as other mechanisms of resistance have been identified, and their role in clinical drug resistance in myelodysplastic syndromes (MDS) and adult acute myeloid leukemia (AML) explored (1,2). In particular, patients with MDS and secondary AML frequently express multidrug transporters that contribute to MDR (3-8). In this chapter, the prevalence and biological and clinical significance of MDR in AML and MDS will be discussed, as well as pharmacological approaches to overcome clinical MDR.