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| Status |
Public on Jun 21, 2022 |
| Title |
Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy 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 |
One day before sample preparation, 293T cells were transfected with pMIGII_3xHA, pMIGII_3xHA-EVI1-WT, or pMIGII_3xHA-EVI1+18 retroviral vector. Detailed protocols for sample preparation were described at: doi.org/10.1016/j.xpro.2021.100404.
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| Contributor(s) |
Tanaka A, Yokoyama A, Kanai A, Inoue D |
| Citation(s) |
35709354 |
| |
| Submission date |
Dec 10, 2021 |
| Last update date |
Jun 25, 2022 |
| Contact name |
Masaki Nomura |
| E-mail(s) |
[email protected]
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| Organization name |
Foundation for Biomedical Research and Innovation at Kobe
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| Street address |
6-3-7 Minatojima Minamimachi, Chuo Ward
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| City |
Kobe |
| State/province |
Hyogo |
| ZIP/Postal code |
650-0047 |
| Country |
Japan |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE190656 |
Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia |
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| Relations |
| BioProject |
PRJNA787927 |
| SRA |
SRP350265 |
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