title: Emerging FMS-like tyrosine kinase 3 inhibitors for the treatment of acute myelogenous leukemia.
abstract: BACKGROUND
  The FMS-like tyrosine kinase 3 (FLT3) is highly expressed in acute leukemias. Mutations involving FLT3 are among the most common molecular abnormalities in acute myelogenous leukemia (AML). Available evidence suggests that these molecular lesions confer a shorter disease-free survival and overall survival in patients with intermediate-risk cytogenetics. Therefore, substantial interest in FLT3 as a therapeutic target has led to the development of several promising inhibitors that target this tyrosine kinase.
  
  
  METHODS
  This review covers the molecular pathways associated with FLT3 activation in patients with AML, the biological rationale for inhibiting FLT3 and recent clinical progress with FLT3 inhibitors for the treatment of AML. Six FLT3 inhibitors undergoing clinical evaluation are discussed. A review of selected published manuscripts on the subject of FLT3 inhibition in AML and a search of the English language manuscripts in PubMed using the index words FLT3 and AML were conducted and articles of interest selected.
  
  
  CONCLUSIONS
  Mutated forms of FLT3, specifically FLT3-internal tandem duplication, have a significant impact on the prognosis of AML patients, particularly those with a normal karyotype. Inhibiting FLT3 may lead to clinical benefit for patients with AML. Newly developed FLT3 inhibitors have shown encouraging activity as monotherapy and in combination with other therapeutic agents.
authors.affiliation: The University of Texas, M.D. Anderson Cancer Center, Department of Leukemia, Houston, USA.
authors.forename: Hillary
authors.initials: H
authors.lastname: Prescott
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D015337:Multicenter Studies as Topic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D051941:fms-Like Tyrosine Kinase 3