title: The clinically relevant pharmacogenomic changes in acute myelogenous leukemia.
abstract: Acute myelogenous leukemia (AML) is an extremely heterogeneous neoplasm with several clinical, pathological, genetic and molecular subtypes. Combinations of various doses and schedules of cytarabine and different anthracyclines have been the mainstay of treatment for all forms of AMLs in adult patients. Although this combination, with the addition of an occasional third agent, remains effective for treatment of some young-adult patients with de novo AML, the prognosis of AML secondary to myelodysplastic syndromes or myeloproliferative neoplasms, treatment-related AML, relapsed or refractory AML, and AML that occurs in older populations remains grim. Taken into account the heterogeneity of AML, one size does not and should not be tried to fit all. In this article, the authors review currently understood, applicable and relevant findings related to cytarabine and anthracycline drug-metabolizing enzymes and drug transporters in adult patients with AML. To provide a prime-time example of clinical applicability of pharmacogenomics in distinguishing a subset of patients with AML who might be better responders to farnesyltransferase inhibitors, the authors also reviewed findings related to a two-gene transcript signature consisting of high RASGRP1 and low APTX, the ratio of which appears to positively predict clinical response in AML patients treated with farnesyltransferase inhibitors.
authors.affiliation: University of Maryland, School of Medicine, Marlene & Stewart Greenebaum Cancer Center, Leukemia & Hematologic Malignancies, Baltimore, MD 21201, USA.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Emadi
authors.forename: Judith E
authors.initials: JE
authors.lastname: Karp
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage*; D004268:DNA-Binding Proteins / Q000235:genetics; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D015201:Meta-Analysis as Topic; D009687:Nuclear Proteins / Q000235:genetics; D010597:Pharmacogenetics; D057285:Precision Medicine
chemical_list: C438188:APTX protein, human; D018943:Anthracyclines; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; C491790:RASGRP1 protein, human; D003561:Cytarabine; D005982:Glutathione Transferase; D051231:Farnesyltranstransferase