Acquired genomic copy number aberrations and survival in adult acute myelogenous leukemia.
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.
Parkin
Brian
B
Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0936, USA.
Erba
Harry
H
Ouillette
Peter
P
Roulston
Diane
D
Purkayastha
Anjali
A
Karp
Judith
J
Talpaz
Moshe
M
Kujawski
Lisa
L
Shakhan
Sajid
S
Li
Cheng
C
Shedden
Kerby
K
Malek
Sami N
SN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005434:Flow Cytometry; D018628:Gene Dosage; D049669:History, 16th Century; D049670:History, 17th Century; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality*; D019656:Loss of Heterozygosity; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
D016159:Tumor Suppressor Protein p53