Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited

J Clin Oncol. 2012 Apr 20;30(12):1343-9. doi: 10.1200/JCO.2011.36.1824. Epub 2012 Feb 27.


Purpose: Interstitial deletions of chromosome 5q are common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), pointing toward the pathogenic role of this region in disease phenotype and clonal evolution. The higher level of resolution of single-nucleotide polymorphism array (SNP-A) karyotyping may be used to find cryptic abnormalities and to precisely define the topographic features of the genomic lesions, allowing for more accurate clinical correlations.

Patients and methods: We analyzed high-density SNP-A karyotyping at diagnosis for a cohort of 1,155 clinically well-annotated patients with malignant myeloid disorders. results: We identified chromosome 5q deletions in 142 (12%) of 1,155 patients and uniparental disomy segments (UPD) in four (0.35%) of 1,155 patients. Patients with deletions involving the centromeric and telomeric extremes of 5q have a more aggressive disease phenotype and additional chromosomal lesions. Lesions not involving the centromeric or telomeric extremes of 5q are not exclusive to 5q- syndrome but can be associated with other less aggressive forms of MDS. In addition, larger 5q deletions are associated with either del(17p) or UPD17p. In 31 of 33 patients with del(5q) AML, either a deletion involving the centromeric and/or telomeric regions or heterozygous mutations in NPM1 or MAML1 located in 5q35 were present.

Conclusion: Our results suggest that the extent of the affected region on 5q determines clinical characteristics that can be further modified by heterozygous mutations present in the telomeric extreme.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Distribution
  • Aged
  • Anemia, Macrocytic / diagnosis
  • Anemia, Macrocytic / epidemiology*
  • Anemia, Macrocytic / genetics*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 5 / genetics
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genomics
  • Hematologic Neoplasms / epidemiology
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / physiopathology
  • Humans
  • Karyotyping
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myeloproliferative Disorders / epidemiology
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / physiopathology
  • Nucleophosmin
  • Point Mutation
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Sex Distribution
  • Statistics, Nonparametric
  • Survival Rate

Supplementary concepts

  • Chromosome 5q Deletion Syndrome