title: AML multi-gene panel testing: A review and comparison of two gene panels.
abstract: OBJECTIVE
  Risk adapted therapy is standard practice in Acute Myeloid Leukemia (AML). A common diagnostic approach involves focusing on a three gene panel (CEPBA, FLT3, and NPM1). However, a complete representation of prognostic and predictive factors in AML necessitates an expanded series of genes, due to the dynamic interactions present between concurrent mutations. Hence, the current study aims to describe the benefits of an expanded risk profile in an unselected cohort of AML cases.
  
  
  METHODS
  The genomes of 11 randomly selected patients with AML were sequenced using next generation sequencing. A narrow three gene panel and broader 50 gene panel were contrasted.
  
  
  RESULTS
  The expanded gene panel detected one additional pathogenic mutation in five patients and two pathogenic mutations in two patients, resulting in a change in their risk profile. Only 5/11 (45%) of AML patients demonstrated a pathogenic mutation on the 3 gene profile, however all patients had at least one detectable pathogenic mutation on the broader gene panel. The detection of a concurrent mutation by the expanded gene panel reversed the favorable risk profile for three patients.
  
  
  CONCLUSIONS
  Detection of concurrent mutations enables rejection or validation of prognoses associated with NPM1 or CEBPA mutations. DNMT3a and TP53 mutations in AML have a pertinent prognostic and therapeutic value for patients and their addition enhances the current three gene panel. In our small study, the three gene panel changed the prognosis for three patients (3/11, 27%) with the detection of commonly occurring AML mutations.
authors.affiliation: University of Hawaii, Department of Pathology, Honolulu, HI, USA. Electronic address: gthakral@hawaii.edu.
authors.forename: G
authors.initials: G
authors.lastname: Thakral
authors.affiliation: University of Hawaii, Department of Pathology, Honolulu, HI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Vierkoetter
authors.affiliation: Hawaii Pathologists' Laboratory, Honolulu, HI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Namiki
authors.affiliation: University of Hawaii, Department of Pathology, Honolulu, HI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lawicki
authors.affiliation: University of Hawaii, Department of Pathology, Honolulu, HI, USA.
authors.forename: X
authors.initials: X
authors.lastname: Fernandez
authors.affiliation: Washington University, St. Louis Missouri, St. Louis, MO, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ige
authors.affiliation: Tufts University, Boston, MA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Kawahara
authors.affiliation: University of Hawaii, Department of Pathology, Honolulu, HI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lum
mesh_terms: D005260:Female; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis
keywords: AML; Detection; Gene panel; Next-generation sequencing; Prognosis; Screening