Transcriptomics

Dataset Information

45

Activation-induced cytidine deaminase accelerates clonal evolution in BCR-ABL1-driven acute lymphoblastic leukemia


ABSTRACT: 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

REANALYSED by: GSE119128

INSTRUMENT(S): [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array

ORGANISM(S): Mus musculus  

SUBMITTER: Markus Muschen  

PROVIDER: GSE16751 | GEO | 2009-06-24

SECONDARY ACCESSION(S): PRJNA117455

REPOSITORIES: GEO

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