title: Molecular Changes During Acute Myeloid Leukemia (AML) Evolution and Identification of Novel Treatment Strategies Through Molecular Stratification.
abstract: Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by impaired differentiation and uncontrollable proliferation of myeloid progenitor cells. Due to high relapse rates, overall survival for this rapidly progressing disease is poor. The significant challenge in AML treatment is disease heterogeneity stemming from variability in maturation state of leukemic cells of origin, genetic aberrations among patients, and existence of multiple disease clones within a single patient. Disease heterogeneity and the lack of biomarkers for drug sensitivity lie at the root of treatment failure as well as selective efficacy of AML chemotherapies and the emergence of drug resistance. Furthermore, standard-of-care treatment is aggressive, presenting significant tolerability concerns to the commonly advanced-age AML patient. In this review, we examine the concept and potential of molecular stratification, particularly with biologically relevant drug responses, in identifying low-toxicity precision therapeutic combinations and clinically relevant biomarkers for AML patient care as a way to overcome these challenges in AML treatment.
authors.affiliation: Institute for Molecular Medicine Finland FIMM, Nordic EMBL Partnership for Molecular Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Karjalainen
authors.affiliation: Institute for Molecular Medicine Finland FIMM, Nordic EMBL Partnership for Molecular Medicine, University of Helsinki, Helsinki, Finland. Electronic address: gretchen.repasky@fimm.fi.
authors.forename: G A
authors.initials: GA
authors.lastname: Repasky
mesh_terms: D003131:Combined Modality Therapy; D018450:Disease Progression; D055808:Drug Discovery; D006801:Humans; D007167:Immunotherapy; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy*; D058990:Molecular Targeted Therapy
keywords: AML; Biomarkers; Combination therapy; Drug resistance; Hematopoietic differentiation; Heterogeneity; Low toxicity; Stratified drug responses; Targeted chemotherapy