PXD034416

PXD034416 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-09 13:11:55	ID requested
⏵ 1	2024-09-30 03:58:32	announced

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;

submitter keyword: AML, MNX1::ETV6, Homeodomain, t(7;12), pediatric AML, MNX1, Methyl-transferases

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/09/PXD034416

PRIDE project URI

• PRIDE
  1. PXD034416
     1. Label: PRIDE project
     2. Name: Mnx1 Induces Leukemia Transformation Through Altering Histone Methylation in a Model of Pediatric t(7;12) Acute Myeloid Leukemia