title: Genetic and epigenetic similarities and differences between childhood and adult AML.
abstract: BACKGROUND
  The biology of acute myeloid leukemia (AML) is complex and includes both genetic and epigenetic aberrations. We addressed the combined consequences of promoter hypermethylation of p15, CDH1, ER, MDR1, and RARB2 and mutation of NPM1, CEBPA, FLT3, and WT1 in a Danish cohort of 70 pediatric and 383 adult AML patients.
  
  
  METHODS
  Mutation analysis was done by fragment analysis followed by sequencing or by sequencing alone. Methylation status was determined using methylation-sensitive melting curve analysis (MS-MCA) after initial bisulfite modification.
  
  
  RESULTS
  Among pediatric AMLs, we found promoter hypermethylation in p15 (47%), CDH1 (64%), ER (62%), MDR1 (8%), and RARB2 (22%) and mutations in NPM1 (11%), CEBPA (3%), FLT3ITD (4%), FLT3D835 (7%), and WT1 (7%). Promoter hypermethylation was significantly more frequent in core binding factor leukemias (CBF) compared to AMLs with abnormalities involving 11q23 (P = 0.024). Compared to adult AML we found a significant difference in p15 (47% vs. 73%, P < 0.001) and RARB2 (22% vs. 42%, P = 0.003) methylation, as well as in NPM1 (11% vs. 31%, P = 0.001) and FLT3ITD (4% vs. 26%, P < 0.001) mutation.
  
  
  CONCLUSIONS
  Age-related differences exist in the frequency of mutations and it appears that promoter hypermethylation occurs in a non-random pattern in childhood AML accompanying specific genetic aberrations, and might represent an important step in the leukemogenic transformation.
authors.affiliation: Department of Hematology, Aarhus University Hospital, Skejby, Denmark.
authors.forename: Caroline
authors.initials: C
authors.lastname: Juhl-Christensen
authors.forename: Hans Beier
authors.initials: HB
authors.lastname: Ommen
authors.forename: Anni
authors.initials: A
authors.lastname: Aggerholm
authors.forename: Birgitte
authors.initials: B
authors.lastname: Lausen
authors.forename: Eigil
authors.initials: E
authors.lastname: Kjeldsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.forename: Peter
authors.initials: P
authors.lastname: Hokland
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics*; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D000090243:Nucleophosmin; D011401:Promoter Regions, Genetic
chemical_list: C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D000090243:Nucleophosmin