Abstract
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic studies have already been published for classical therapies, such as cytarabine or anthracyclines, but such studies remain scarce for newer drugs. There is evidence of the relevance of polymorphisms in response to treatment, although most studies have limitations in terms of cohort size or standardization of results. The different responses associated with genetic variability include both increased drug efficacy and toxicity and decreased response or resistance to treatment. A broad pharmacogenetic understanding may be useful in the design of dosing strategies and treatment guidelines. The aim of this study is to perform a review of the available publications and evidence related to the pharmacogenetics of AML, compiling those studies that may be useful in optimizing drug administration.
Highlights
Acute myeloid leukemia (AML) encompasses a broad and diverse group of aggressive blood cell tumors arising from the uncontrolled spread of tumor hematopoietic precursor cells in the bone marrow
Cytarabine is an antineoplastic agent indicated for initial induction and maintenance therapy in AML
These drugs block the action of mutated forms of isocitrate dehydrogenase (IDH) that occur in 15–20% of patients [86]
Summary
Acute myeloid leukemia (AML) encompasses a broad and diverse group of aggressive blood cell tumors arising from the uncontrolled spread of tumor hematopoietic precursor cells in the bone marrow. Five-year relative survival after diagnosis of AML is estimated at 18% in Europe [1]. In Spain, the five-year relative survival has been estimated to be around 20% [2]. There is high toxicity associated with chemotherapy and high rates of relapse and resistance in elderly patients [4]. Exposure to chemotherapy regimens places enormous stress on AML cell populations and may be more toxic to certain cell clones than others. It has been observed that the clonal composition of AML change markedly after therapy in relapsed disease, with selection occurring at both the genetic and epigenetic levels [6]. Patient-related factors (e.g., advanced age, coexisting diseases or poor performance status) usually predict early death, whereas disease-related factors (e.g., prior myelodysplastic syndrome, prior exposure to cytotoxic or radiation therapy or cytogenetic and/or molecular findings in leukemic cells) predict resistance to current standard therapy or early relapse
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