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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
|
| 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 |
Examination of different DNA binding of EVI1 in 3q-rearranged hematopoietic cells with or without SF3B1 mutations .
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| Contributor(s) |
Nomura M, Delwel R, Inoue D, Abdel-Wahab O |
| Citation(s) |
35709354 |
| |
| Submission date |
May 04, 2022 |
| Last update date |
Jun 25, 2022 |
| Contact name |
Masaki Nomura |
| E-mail(s) |
[email protected]
|
| Organization name |
Foundation for Biomedical Research and Innovation at Kobe
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| 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) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (8)
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| GSM6106330 |
input_Molm1_140616_SN583_0116_AH7PJVADXX |
| GSM6106331 |
EVI1_Molm1_140415_SN583_0110_AC3UTLACXX |
| GSM6106332 |
EVI1_input_HNT34_141211_SN583_0132_AC66ATACXX |
| GSM6106333 |
EVI1_HNT34_141211_SN583_0132_AC66ATACXX |
| GSM6106334 |
EVI1_input_MUTZ3_141211_SN583_0132_AC66ATACXX |
| GSM6106335 |
EVI1_MUTZ3_141211_SN583_0132_AC66ATACXX |
| GSM6106336 |
input_2747_140616_SN583_0116_AH7PJVADXX |
| GSM6106337 |
EVI1_2747_140519_SN583_0115_AH7CFPADXX |
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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 |
PRJNA835058 |
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