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Series GSE16751 Query DataSets for GSE16751
Status Public on Jun 24, 2009
Title Activation-induced cytidine deaminase accelerates clonal evolution in BCR-ABL1-driven acute lymphoblastic leukemia
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
Overall design We used microarrays to detect differences in gene expression profiles between AID expressing leukemia and AID deficient leukemia
Contributor(s) Gruber TA, Muschen M
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Submission date Jun 23, 2009
Last update date Feb 11, 2019
Contact name Markus Muschen
Organization name Childrens Hospital Los Angeles
Department Hematology Oncology
Lab Muschen
Street address 4650 Sunset Blvd MS 136
City Los Angeles
State/province CA
ZIP/Postal code 90027
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (6)
GSM419953 AID-/- leukemia biological replicate 1
GSM419954 AID-/- leukemia biological replicate 2
GSM419955 AID-/- leukemia biological replicate 3
BioProject PRJNA117455

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Supplementary file Size Download File type/resource
GSE16751_RAW.tar 21.1 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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