Unknown,Transcriptomics,Genomics,Proteomics

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Diagnosis-relapse in ALL


ABSTRACT: Almost a quarter of pediatric patients with Acute Lymphoblastic Leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis relapse pairs of ALL patients using genomeâ??wide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients very few differences between diagnosis and relapse samples were found (â??stable groupâ??), suggesting that mostly extra-leukemic factors (e.g., drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 samples with clear differences in gene expression (â??skewed groupâ??), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of relapses are due to selection or emergence of a clone with deregulated expression of a genes involved in pathways that regulate B cell signaling, development, cell cycle, cellular division and replication. The study contains 41 pairs of samples taken from patients at diagnosis and relapse (a total of 82 arrays).

ORGANISM(S): Homo sapiens

SUBMITTER: Dick de Ridder 

PROVIDER: E-GEOD-18497 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide expression analysis of paired diagnosis-relapse samples in ALL indicates involvement of pathways related to DNA replication, cell cycle and DNA repair, independent of immune phenotype.

Staal F J T FJ   de Ridder D D   Szczepanski T T   Schonewille T T   van der Linden E C E EC   van Wering E R ER   van der Velden V H J VH   van Dongen J J M JJ  

Leukemia 20100114 3


Almost a quarter of pediatric patients with acute lymphoblastic leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis-relapse pairs of ALL patients using genome-wide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients, very few differences between diagnosis and relapse samples were f  ...[more]

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