Acquired genomic copy number aberrations and survival in adult acute myelogenous leukemia.
Posted by rob on August 24, 2010 under Uncategorized | 
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Acquired genomic copy number aberrations and survival in adult acute myelogenous leukemia.
Blood. 2010 Aug 20;
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
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 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. Here, we have analyzed FACS-sorted AML blast-derived and paired buccal DNA from 114 previously untreated prospectively enrolled AML patients for acquired genomic copy number changes and LOH using Affymetrix SNP 6.0 arrays, and we have 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 have identified an independent negative prognostic impact of p53 mutations, or p53 mutations and 17p-LOH combined on survival in AML.
PMID: 20729466 [PubMed - as supplied by publisher]