Acquired genomic copy number aberrations and survival in adult acute myelogenous leukemia.

Published

Journal Article

Genomic aberrations are of predominant importance to the biology and clinical outcome of patients with acute myelogenous leukemia (AML), and conventional karyotype-based risk classifications are routinely used in clinical decision making in AML. One of the known limitations of cytogenetic analysis is the inability to detect genomic abnormalities less than 5 Mb in size, and it is currently unclear whether overcoming this limitation with high-resolution genomic single-nucleotide polymorphism (SNP) array analysis would be clinically relevant. Furthermore, given the heterogeneity of molecular mechanisms/aberrations that underlie the conventional karyotype-based risk classifications, it is likely that further refinements in genomic risk prognostication can be achieved. In this study, we analyzed flow cytometer-sorted, AML blast-derived, and paired, buccal DNA from 114 previously untreated prospectively enrolled AML patients for acquired genomic copy number changes and loss of heterozygosity using Affymetrix SNP 6.0 arrays, and we correlated genomic lesion load and specific chromosomal abnormalities with patient survival. Using multivariate analyses, we found that having ≥ 2 genomic lesions detected through SNP 6.0 array profiling approximately doubles the risk of death when controlling for age- and karyotype-based risk. Finally, we identified an independent negative prognostic impact of p53 mutations, or p53 mutations and 17p-loss of heterozygosity combined on survival in AML.

Full Text

Duke Authors

Cited Authors

  • Parkin, B; Erba, H; Ouillette, P; Roulston, D; Purkayastha, A; Karp, J; Talpaz, M; Kujawski, L; Shakhan, S; Li, C; Shedden, K; Malek, SN

Published Date

  • December 2, 2010

Published In

Volume / Issue

  • 116 / 23

Start / End Page

  • 4958 - 4967

PubMed ID

  • 20729466

Pubmed Central ID

  • 20729466

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2010-01-266999

Language

  • eng

Conference Location

  • United States