Transcriptomics

Dataset Information

6

Clonal evolution and devolution following chemotherapy in adult acute myelogenous leukemia


ABSTRACT: The frequent occurrence of persistent or relapsed disease following induction chemotherapy in AML necessitates a better understanding of the clonal relationship of AML in various disease phases. In this study, we employed SNP 6.0 array-based genomic profiling of acquired copy number aberrations (aCNA) and copy neutral LOH (cnLOH) together with sequence analysis of recurrently mutated genes to characterize paired AML genomes. We analyzed 28 AML sample pairs from patients that achieved complete remission with chemotherapy and subsequently relapsed and 11 sample pairs from patients with persistent disease following induction chemotherapy. Through review of aCNA/cnLOH and gene mutation profiles in informative cases we demonstrate that relapsed AML invariably represents reemergence or evolution of a founder clone. Furthermore, all individual aCNA or cnLOH detected at presentation persisted at relapse indicating that this lesion type is proximally involved in AML evolution. Analysis of informative paired persistent AML disease samples uncovered cases with two coexisting dominant clones of which at least one was chemotherapy sensitive and one resistant, respectively. These data support the conclusion that incomplete eradication of AML founder clones rather than stochastic emergence of fully unrelated novel clones underlies AML relapse and persistence with direct implications for clinical AML research This study is based on 39 patients with AML for which either paired enrollment or relapse samples or persistent disease samples were available. The patients were enrolled into this study at the University of Michigan Comprehensive Cancer Center. The study was approved by the University of Michigan Institutional Review Board (IRBMED #2004-1022) and written informed consent was obtained from all patients prior to enrollment. Genomic DNA was extracted from purified AML blasts and paired buccal cells. DNA thus obtained was hybridized to Affymetrix SNP 6.0 arrays. Note: There is no normal sample available for MIAML015.

ORGANISM(S): Homo sapiens  

SUBMITTER: Peter Ouillette   Brian Parkin  Diane Roulston  Sami N Malek  Jennifer Keller  Cheng Li  Cindy Lam  Yifeng Li  Sami N Malek  Kerby Shedden 

PROVIDER: E-GEOD-41646 | ArrayExpress | 2013-02-12

SECONDARY ACCESSION(S): GSE41646PRJNA177821

REPOSITORIES: GEO, ArrayExpress

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Publications

Clonal evolution and devolution after chemotherapy in adult acute myelogenous leukemia.

Parkin Brian B   Ouillette Peter P   Li Yifeng Y   Keller Jennifer J   Lam Cindy C   Roulston Diane D   Li Cheng C   Shedden Kerby K   Malek Sami N SN  

Blood 20121121 2


The frequent occurrence of persistent or relapsed disease after induction chemotherapy in AML necessitates a better understanding of the clonal relationship of AML in various disease phases. In this study, we used SNP 6.0 array-based genomic profiling of acquired copy number aberrations (aCNA) and copy neutral LOH (cnLOH) together with sequence analysis of recurrently mutated genes to characterize paired AML genomes. We analyzed 28 AML sample pairs from patients who achieved complete remission w  ...[more]

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