title: Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3) inhibitor therapy with evolving actionable targets.
abstract: For acute myeloid leukemia (AML), identification of activating mutations in the FMS-like tyrosine kinase-3 (FLT3) has led to the development of several FLT3-inhibitors. Here we present clinical and next generation sequencing data at the time of progression of a patient on a novel FLT3-inhibitor clinical trial (ASP2215) to show that employing therapeutic interventions with these novel targeted therapies can lead to consequences secondary to selective pressure and clonal evolution of cancer. We describe novel findings alongside data on treatment directed towards actionable aberrations acquired during the process. (
  
  
  BACKGROUND
  NCT02014558; registered at: 〈https://clinicaltrials.gov/ct2/show/NCT02014558〉).
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Pashtoon M
authors.initials: PM
authors.lastname: Kasi
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Mrinal M
authors.initials: MM
authors.lastname: Patnaik
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Shahrukh K
authors.initials: SK
authors.lastname: Hashmi
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Naseema
authors.initials: N
authors.lastname: Gangat
keywords: ASP2215; Acute Leukemia; Clonal evolution; FMS-like tyrosine kinase-3 (FLT3) inhibitors; Philadelphia chromosome (BCR-ABL); Ponatinib