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| Status |
Public on Jun 21, 2022 |
| Title |
Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia (RNA-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Detailed genomic and epigenomic analyses of MECOM (the MDS1 and EVI1 complex locus) have revealed that inversion or translocation of chromosome 3 at MECOM drive inv(3)/t(3;3) myeloid leukemias and revealed MECOM germline mutations in patients with MECOM-associated bone marrow failure syndromes. Here we identify a novel, previously unannotated oncogenic RNA-splicing derived isoform of EVI1 which is frequently present in inv(3)/t(3;3) AML and directly contributes to leukemic transformation. Expression of this EVI1 splice variant enhanced the self-renewal of hematopoietic stem cells and introduction of mutant SF3B1 in mice bearing the humanized inv(3)(q21;26) allele hastened leukemogenesis in vivo. These data provide a mechanistic basis for the frequent co-occurrence of SF3B1 mutations as well as new insights into the pathogenesis of myeloid leukemias harboring inv(3)/t(3;3).
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| Overall design |
mRNA profiles of wild type mouse hematopoietic stem or progenitor cells expressing EVI1-WT or EVI1+18.
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| Contributor(s) |
Tanaka A, Zang W, Nomura M, Inoue D, Abdel-Wahab O |
| Citation(s) |
35709354 |
| |
| Submission date |
May 04, 2022 |
| Last update date |
Jun 21, 2022 |
| Contact name |
Masaki Nomura |
| E-mail(s) |
masaki.nomura.fbri@gmail.com
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| Organization name |
Foundation for Biomedical Research and Innovation at Kobe
|
| Street address |
6-3-7 Minatojima Minamimachi, Chuo Ward
|
| City |
Kobe |
| State/province |
Hyogo |
| ZIP/Postal code |
650-0047 |
| Country |
Japan |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE202211 |
Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia II |
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| Relations |
| BioProject |
PRJNA835057 |
