title: Conserved hierarchical gain of chromosome 4 is an independent prognostic factor in high hyperdiploid pediatric acute lymphoblastic leukemia.
abstract: BACKGROUND
  High hyperdiploid (HeH) pre-B pediatric acute lymphoblastic leukemia (B-pALL) is known to be heterogeneous by prognosis, but the stratification principals according to conventional cytogenetic analysis (CCA) are equivocal.
  
  
  METHODS
  Untreated bone marrow samples of 214 B-pALL patients were previously classified according to the modal numbers (iMN8) based on the gains of the chromosomes 4, 6, 10, 14, 17, 18, 21, and X as revealed by consecutive and correlated 2×4 color interphase fluorescence in situ hybridization, and at least five years of follow up data were analyzed.
  
  
  RESULTS
  Data from 48 of the 53 HeH (iMN8>50) B-pALL patients indicated that among the age, gender, WBC, and iMN8parameters, only the last was significantly associated with overall survival (pOS), which allowed the cases to be classified as iMN851-54 (75%) and iMN8≥ 55 (95%). Among the specific chromosomal gains of +4, +4/+6, +4/+17 and +4/+18, the first exhibited the most significance in terms of beneficial outcomes. The better prognostic group according to the iMN8was associated with a significantly reduced complexity of the subclonal landscape. However, iMN8did not prove to be an independent variable but was instead overridden by isolated trisomy of chromosome 4.
  
  
  CONCLUSIONS
  These data indicate that the better outcomes in the HeH B-pALL group arose from the gain of a specific chromosome that always ranks at the same position in the sequential acquisition of the affected chromosomes.
authors.affiliation: Pediatric Oncology Unit.
authors.forename: Á
authors.initials: Á
authors.lastname: Vojcek
authors.affiliation: Department of Pathology.
authors.forename: G
authors.initials: G
authors.lastname: Pajor
authors.affiliation: Department of Pathology.
authors.forename: D
authors.initials: D
authors.lastname: Alpár
authors.affiliation: Department of Translational Medicine.
authors.forename: R
authors.initials: R
authors.lastname: Mátics
authors.affiliation: Department of Bioanalysis of the University of Pécs Medical Center, Pécs, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Pótó
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Szuhai
authors.affiliation: Department of Pathology. Electronic address: lpajor54@yahoo.com.
authors.forename: L
authors.initials: L
authors.lastname: Pajor
mesh_terms: D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D004171:Diploidy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D016019:Survival Analysis; D014314:Trisomy
keywords: Hyperdiploidy; Lymphoblastic leukemia; Prognosis; iFISH