Transcriptomics

Dataset Information

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Identification of a Potently Oncogenic CALM-AF10 Minimal-Fusion Mutant (miRNA)


ABSTRACT: The t(10;11) p (13;q14) translocation, giving rise to CALM-AF10, is a recurring chromosomal translocation observed in several types of acute leukemias as well as in lymphoma. We have previously demonstrated that the expression of the human CALM/AF10 fusion gene in murine bone marrow stem and progenitor cells results in an aggressive acute myeloid leukemia in vivo. In this study, we have screened the various domains essential for CALM-AF10 function and leukemogenicity. Our study identifies a mutant of CALM-AF10 that greatly enhances the clonogenic potential of hematopoietic progenitors while retaining key characteristics of disease induced by the full length CALM-AF10 fusion. Global micro-RNA expression of bone marrow cells transduced with various constructs were compared. We used the empty vector, MIG, as a control and baseline. Four samples are tested with three biological replicates each.

ORGANISM(S): Mus musculus  

SUBMITTER: Aniruddha J Deshpande  Karlheinz Holzmann     Sabrina Opatz   Philipp Greif   Arefeh Rouhi   Stefan K Bohlander   Yihui Lin   Christian Buske   Leticia Quintanilla-Fend   Wolfgang Hiddemann   Natalia Arseni   Karlheinz Holzmann   Guoliang Xu   Christiane Stadler   Scott Armstrong    

PROVIDER: E-GEOD-27512 | ArrayExpress | 2011-10-04

SECONDARY ACCESSION(S): GSE27512PRJNA141867

REPOSITORIES: GEO, ArrayExpress

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Publications

The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice.

Deshpande A J AJ   Rouhi A A   Lin Y Y   Stadler C C   Greif P A PA   Arseni N N   Opatz S S   Quintanilla-Fend L L   Holzmann K K   Hiddemann W W   Döhner K K   Döhner H H   Xu G G   Armstrong S A SA   Bohlander S K SK   Buske C C  

Leukemia 20110617 11


The t(10;11)(p13-14;q14-21) translocation, giving rise to the CALM-AF10 fusion gene, is a recurrent chromosomal rearrangement observed in patients with poor prognosis acute myeloid leukemia (AML). Although splicing of the CALM-AF10 fusion transcripts has been described in AML patients, the contribution of different CALM and AF10 domains to in vivo leukemogenesis remains to be defined. We therefore performed detailed structure-function studies of the CALM-AF10 fusion protein. We demonstrate that  ...[more]

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