Genome scan implicates adhesion biological pathways in secondary leukemia.

Genome scan implicates adhesion biological pathways in secondary leukemia. Research Abstract Details 

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Genome scan implicates adhesion biological pathways in secondary leukemia. Abstract Text:

C Hartford,W Yang,C Cheng,Y Fan,W Liu,L ,S Pounds,G Neale,S C Raimondi,A Bogni,M E Dolan,C-H Pui,M V Relling,

The genetic risk factors for etoposide-induced leukemia with MLL translocations remain largely unknown. To identify genetic risk factors for and novel characteristics of secondary leukemia, we profiled 116,204 single nucleotide polymorphisms (SNPs) in germline and paired leukemic cell DNA from 13 secondary leukemia/myelodysplasia cases and germline DNA from 13 matched and 156 unmatched controls, all with acute lymphoblastic leukemia treated with etoposide. We analyzed global gene expression from a partially overlapping cohort. No single locus was altered in most cases. We discovered 81 regions of loss of heterozygosity (LOH) in leukemic blasts and 309 SNPs whose allele frequencies differed in cases vs controls. Candidate genes were prioritized on the basis of genes whose SNPs or expression differentiated cases from controls or showed LOH or copy number change in germline vs paired blast DNA from the 13 cases. Three biological pathways were altered: adhesion, Wnt signaling and regulation of actin. Validation experiments using a genome scan for etoposide-induced leukemogenic MLL chimeric fusions in 15 HapMap cell lines also implicated genes involved in adhesion, a process linked to de novo leukemogenesis. Independent clinical epidemiologic and in vitro genome-wide approaches converged to identify novel pathways that may contribute to therapy-induced leukemia.

Genome scan implicates adhesion biological pathways in secondary leukemia. Publishing Authors By Initials

C Hartford,W Yang,C Cheng,Y Fan,W Liu,L ,S Pounds,G Neale,SC Raimondi,A Bogni,ME Dolan,CH Pui,MV Relling,

For similar pathological conditions, signs and symptoms: pathologic processes: chromosome aberrations: translocation, genetic research abstracts see: pathological conditions, signs and symptoms: pathologic processes: chromosome aberrations: translocation, genetic research

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Genome scan implicates adhesion biological pathways in secondary leukemia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Leukemia : official journal of the Leukemia Societ

VOLUME: 21

Page Numbers: 2128-36

Journal Abbreviation: Leukemia

ISSN: 0887-6924

DAY: 2

MONTH: 08

YEAR: 2007

Genome scan implicates adhesion biological pathways in secondary leukemia. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8704895

Genome scan implicates adhesion biological pathways in secondary leukemia. Keywords Mesh Terms:

KEYWORDS: Translocation, Genetic

MESH TERMS: pathology

Chemical & Substance for Abstract: Genome scan implicates adhesion biological pathways in secondary leukemia. Information

Substance Name: Etoposide

Registry Number: 33419-42-0

Grant and Affiliation Information for Genome scan implicates adhesion biological pathways in secondary leukemia.

AFFILIATION: Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.

Country: England

AGENCY: United States NIGMS

GRANT: U01GM61374

ACRONYM: GM

MEDLINETA: Leukemia

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