title: Prognostic significance of acquired copy-neutral loss of heterozygosity in acute myeloid leukemia.
abstract: BACKGROUND
  Chromosomal abnormalities are important in the diagnosis and prognosis of patients with acute myeloid leukemia (AML). Genomic microarray techniques detect recurrent copy-neutral loss of heterozygosity (cnLOH) in addition to copy number aberrations. However, the clinical utility has not been fully established. Therefore, in the current study, the authors examined the prognostic impact of acquired cnLOH in patients with AML, including complete remission (CR) rate, duration of CR, and overall survival (OS).
  
  
  METHODS
  A total of 112 consecutive patients with AML who were undergoing chromosome genomic array testing (CGAT) at the Seattle Cancer Care Alliance were included in the current study. DNA from the bone marrow or blood was analyzed with a microarray platform with both single-nucleotide polymorphism (SNP) probes and non-SNP probes to identify acquired cnLOH. Results were correlated with cytogenetic, molecular, immunophenotypic, and other clinicopathological findings.
  
  
  RESULTS
  Patients with cnLOH demonstrated a shorter duration of CR (hazard ratio, 1.87; P =.04) and worse OS (HR, 1.82; P = .03). Multivariate analyses confirmed the independent predictive value of cnLOH for early disease recurrence (P =.02). These results largely reflected those in patients with intermediate and unfavorable cytogenetics. Most strikingly, 13q cnLOH was found to demonstrate a 6.64-fold higher rate of disease recurrence (P =.006) and 3.45-fold worse OS (P = .02) and was enriched with the FLT3-ITD (Fms-related tyrosine kinase 3-internal tandem duplication) mutation.
  
  
  CONCLUSIONS
  CnLOH has important prognostic significance in patients with AML. CGAT can replace imbalance fluorescence in situ hybridization and the authors recommend the routine use of CGAT to detect cnLOH, particularly among patients with intermediate-risk cytogenetics.
authors.affiliation: Cytogenetics Department, Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gronseth
authors.affiliation: Cytogenetics Department, Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Scott E
authors.initials: SE
authors.lastname: McElhone
authors.affiliation: Clinical Statistics Department, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.affiliation: Cytogenetics Department, Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Kroeger
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Vicky
authors.initials: V
authors.lastname: Sandhu
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Medicine, University of Washington, Seattle, Washington.|Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Fero
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Medicine, University of Washington, Seattle, Washington.|Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Medicine, University of Washington, Seattle, Washington.|Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Pathology, University of Washington, Seattle, Washington.|Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D055815:Young Adult
keywords: acute myeloid leukemia (AML); chromosome genomic array testing (CGAT); copy-neutral loss of heterozygosity (cnLOH); prognosis