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PXD008213

PXD008213 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKMT2A-rearranged leukemia proteomics
DescriptionActivating mutations in kinase/PI3K/RAS signaling pathways are common in acute leukemia with KMT2A rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remain unclear. Using a retroviral acute myeloid leukemia model, we demonstrate that NRASG12D, FLT3ITD, and FLT3N676K accelerates KMT2A-MLLT3 leukemia onset. Importantly, also the presence of subclonal FLT3N676K in KMT2A-R leukemic cells shorten disease latency, possibly by providing stimulatory factors such as Mif. Acquired de novo mutations in Braf, Cbl, Kras, and Ptpn11 were identified in KMT2A-MLLT3 driven leukemia and favored clonal expansion. KMT2A-MLLT3 leukemia with an activating mutation enforce Myc- and Myb transcriptional modules, whereas KMT2A-MLLT3 leukemias lacking activating mutations displayed upregulation of signal transduction pathways. Our results provide new insight into the biology of KMT2A-R leukemia and highlights the importance of activated signaling as a contributing driver in this disease.
HostingRepositoryPRIDE
AnnounceDate2019-03-06
AnnouncementXMLSubmission_2019-03-06_02:11:21.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJenny Hansson
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-11-15 01:21:20ID requested
12018-05-01 23:46:20announced
22018-05-07 00:04:22announcedUpdated publication reference for PubMed record(s): 29720585.
32018-05-07 00:59:19announcedUpdated project metadata.
42019-03-06 02:11:22announcedUpdated project metadata.
Publication List
Hyrenius-Wittsten A, Pilheden M, Sturesson H, Hansson J, Walsh MP, Song G, Kazi JU, Liu J, Ramakrishan R, Garcia-Ruiz C, Nance S, Gupta P, Zhang J, R, ö, nnstrand L, Hultquist A, Downing JR, Lindkvist-Petersson K, Paulsson K, J, ä, r, å, s M, Gruber TA, Ma J, Hagstr, ö, m-Andersson AK, De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia. Nat Commun, 9(1):1770(2018) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: Mouse, leukemia, TMT
Contact List
Jenny Hansson
contact affiliationDivision of Molecular Hematology, Department of Laboratory Medicine, Lund University
contact emailjenny.hansson@med.lu.se
lab head
Jenny Hansson
contact affiliationLund University
contact emailjehansson@gmail.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
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