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E-GEOD-16751 - Transcription profiling of AID expressing leukemia and AID deficient leukemia in a mouse model of BCR-ABL1 ALL

Status
Submitted on 23 June 2009, released on 5 July 2009, last updated on 10 June 2011
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (5)
Description
Activation-Induced Cytidine Deaminase (AID) is required for somatic hypermutation and immunoglobulin (Ig) class switch recombination in germinal center B lymphocytes. Occasionally, AID targets non-Ig genes, thereby contributing to B cell lymphomagenesis. We recently reported aberrant expression of AID in BCR-ABL1-driven acute lymphoblastic leukemia (ALL). To elucidate the biological significance of aberrant AID expression, we studied loss of AID function in a murine model of BCR-ABL1 ALL. Mice transplanted with BCR-ABL1-transduced AID-/- bone marrow had prolonged survival as compared to mice transplanted with leukemia cells generated from AID+/+ bone marrow. Consistent with a causative role of AID in genetic instability, AID-/- leukemia had a decreased frequency of amplifications, deletions and a lower frequency of mutations in non-Ig genes including Pax5 and Rhoh as compared to AID+/+ leukemias. AID-/- and AID+/+ ALL cells showed a markedly distinct gene expression pattern as determined by principle component analysis, with 2,365 genes differentially expressed. In contrast to AID+/+ leukemia, AID-/- ALL cells failed to downregulate a number of tumor suppressor genes such as Rhoh, Cdkn1a (p21), and Blnk (SLP65). We conclude that AID accelerates clonal evolution in BCR-ABL1 ALL by enhancing genetic instability, aberrant somatic hypermutation, and by transcriptional inactivation of tumor suppressor genes. Experiment Overall Design: We used microarrays to detect differences in gene expression profiles between AID expressing leukemia and AID deficient leukemia
Experiment types
transcription profiling by array, unknown experiment type
Contact
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-16751.idf.txt
Sample and data relationshipE-GEOD-16751.sdrf.txt
Raw data (1)E-GEOD-16751.raw.1.zip
Processed data (1)E-GEOD-16751.processed.1.zip
Array designA-AFFY-45.adf.txt
R ExpressionSetE-GEOD-16751.eSet.r
Links