PXD034416 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mnx1 Induces Leukemia Transformation Through Altering Histone Methylation in a Model of Pediatric t(7;12) Acute Myeloid Leukemia |
Description | Acute myeloid leukemia (AML) in children with cytogenetic aberrations like translocation t(7;12)(q36;p13) is associated with inferior outcome. The translocation can lead to a fusion transcript MNX1::ETV6 but also to activation of MNX1 transcription. We generated an AML mouse model by transplantation of fetal liver cells with ectopic expression of MNX1. AML was highly penetrant in immunocompromised and less penetrant in immunocompetent mice. Transforming capacity was restricted to fetal liver cells and could not achieved with adult bone marrow cells, in concordance with the clinical finding that t(7;12)(q36;p13) is mostly restricted to infants. Ectopic expression of MNX1 led to increased H3K4methylation and reduced H3K27me3, possibly through its interaction with methyl transferases. MNX1 expression was accompanied with changes in genome wide chromatin accessibility , increased DNA damage, depletion in the LSK population and skewing toward the myeloid lineage. These effects, together with leukemia development, could be prevented by the S-adenosylmethionine analogue Sinefungin that acts as a SAM competitor and a pan methyltranferases inhibitor. Expression profiles of a human iPSC AML model with t(7;12) and of TARGET pediatric AML and TCGA patients support the rationale for targeting MNX1 and downstream pathways. |
HostingRepository | PRIDE |
AnnounceDate | 2024-09-30 |
AnnouncementXML | Submission_2024-09-30_03:58:27.626.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Johannes Fuchs |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-06-09 13:11:55 | ID requested | |
⏵ 1 | 2024-09-30 03:58:32 | announced | |
Publication List
Waraky A, Ö, stlund A, Nilsson T, Weichenhan D, Lutsik P, B, ä, hr M, Hey J, Tunali G, Adamsson J, Jacobsson S, Morsy MHA, Li S, Fogelstrand L, Plass C, Palmqvist L, Aberrant MNX1 expression associated with t(7;12)(q36;p13) pediatric acute myeloid leukemia induces the disease through altering histone methylation. Haematologica, 109(3):725-739(2024) [pubmed] |
10.3324/haematol.2022.282255; |
Keyword List
submitter keyword: AML, MNX1::ETV6, Homeodomain, t(7;12), pediatric AML, MNX1, Methyl-transferases |
Contact List
Lars Palmqvist |
contact affiliation | Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, and 2Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden |
contact email | lars.palmqvist@clinchem.gu.se |
lab head | |
Johannes Fuchs |
contact affiliation | Gothenburg University |
contact email | johannes.fuchs@gu.se |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD034416
- Label: PRIDE project
- Name: Mnx1 Induces Leukemia Transformation Through Altering Histone Methylation in a Model of Pediatric t(7;12) Acute Myeloid Leukemia