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| Status |
Public on Jun 21, 2022 |
| Title |
Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia [mouse_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 |
1.0 x 10E6 total BM cells of Mx1-Cre control, Mx1-Cre inv(3), Mx1-Cre Sf3b1K700E/WT, and Mx1-Cre inv(3) Sf3b1K700E/WT CD45.2+ mice were mixed with 1.0 x 10E6 WT CD45.1+ support BM and transplanted via tail vein injection into lethally irradiated (two times 450 cGy) CD45.1+ recipient mice. Four weeks after BMT, the recipient mice received 20 mg/kg pIpC injection every other day for a total of 3 doses. Six months after pIpC injection, the recipient mice were sacrificed for sample preparation.
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| Contributor(s) |
Penson A, Nomura M, Inoue D, Abdel-Wahab O |
| 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) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (12)
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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 |
PRJNA787924 |
| SRA |
SRP350270 |
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