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

Content Provider	PubMed Central
Author	Parkin, Brian Erba, Harry Ouillette, Peter Roulston, Diane Purkayastha, Anjali Karp, Judith Moshe, Talpaz Kujawski, Lisa Sajid, Shakhan Li, Cheng Shedden, Kerby Malek, Sami N.
Abstract	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.
Related Links	http://dx.doi.org/10.1182/blood-2010-01-266999
Ending Page	4967
Page Count	10
Starting Page	4958
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	23
Volume Number	116
Language	English
Publisher	American Society of Hematology
Publisher Date	2010-12-02
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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