title: Changes in cytogenetics and molecular genetics in acute myeloid leukemia from childhood to adult age groups.
abstract: BACKGROUND
  To obtain better insight into the biology of acute myeloid leukemia (AML) in various age groups, this study focused on the genetic changes occurring during a lifetime.
  
  
  METHODS
  This study analyzed the relation between age and genetics from birth to 100 years in 5564 patients with de novo AML diagnosed from 1998 to 2012 (1192 patients from nationwide pediatric studies [AML Berlin-Frankfurt-Münster studies 98 and 2004] and 4372 adults registered with the Munich Leukemia Laboratory).
  
  
  RESULTS
  The frequencies of cytogenetic subgroups were age-dependent. Favorable subtypes (t(8;21), inv(16)/t(16;16), and t(15;17)) decreased in general from the pediatric age group (2 to < 18 years; 33%) to the oldest groups (<5% for > 70 years; P < .0001). Unfavorable cytogenetics (-7/del(7), -5/del(5q) or 5p, inv(3)/t(3;3), t(6;9), complex karyotype, 12p, 17p, and 11q23/mixed-lineage leukemia aberrations, excluding t(9;11)) were frequent (42%) in infants (<2 years), had a low frequency in children and young adults (<22%), and increased in frequency up to 36% in patients older than 85 years (P = .01). This was even more significant for complex karyotypes (P ≤ .0001), which also showed a strong increase in the absolute age-specific incidence with age. Interestingly, the frequency of 11q23 abnormalities decreased from infants to older patients. The proportion of clinically relevant molecular aberrations of CCAAT/enhancer binding protein α, nucleophosmin (NPM1), and NPM1/fms-related tyrosine kinase 3-internal tandem duplication increased with age.
  
  
  CONCLUSIONS
  Altogether, with the exclusion of infants, a significant decrease in the proportion of favorable cytogenetic subtypes and an increase in unfavorable cytogenetics were observed with increasing age. These findings indicate different mechanisms for the pathogenesis of AML; these different mechanisms also suggest directions for etiological research and contribute to the more unfavorable prognosis with increasing age. Cancer 2016;122:3821-3830. © 2016 American Cancer Society.
authors.affiliation: Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.affiliation: Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.affiliation: Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Rasche
authors.affiliation: Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: von Neuhoff
authors.affiliation: Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Alpermann
authors.affiliation: Department of Pediatrics, St. Anna Children's Hospital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Dworzak
authors.affiliation: Munich Leukemia Laboratory 2 SRO, Prague, Czech Republic.
authors.forename: Karolína
authors.initials: K
authors.lastname: Perglerová
authors.affiliation: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zemanova
authors.affiliation: Pediatric Hematology/Oncology, University of Zurich, Zurich, Switzerland.
authors.forename: Joelle
authors.initials: J
authors.lastname: Tchinda
authors.affiliation: Institute for Pathology, University Hospital of Giessen and Marburg, Giessen, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Bradtke
authors.affiliation: Medical Clinic and Policlinic I, Carl Gustav Carus University Hospital, Technical University, Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis / Q000379:methods; D003582:Cytogenetics / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology / Q000379:methods; D000090243:Nucleophosmin; D011379:Prognosis; D055815:Young Adult
keywords: acute myeloid leukemia; adults; age groups; cytogenetics; molecular genetics; pediatric