PXD001994

PXD001994 is an original dataset announced via ProteomeXchange.

Title	miR-126 Governs Human Leukemia Stem Cell Quiescence and Therapeutic Resistance
Description	In acute myeloid leukemia (AML), leukemia stem cells (LSC) play a central role in disease progression and recurrence due to their intrinsic capacity for self-renewal and chemotherapy resistance. Whereas epigenetic mechanisms balance normal blood stem cell self-renewal and fate decisions, mutation and dysregulation of epigenetic regulators are considered fundamental to leukemia initiation and progression. Alterations in miRNA function represent a non-canonical epigenetic mechanism influencing malignant hematopoiesis, however the function of miRNA in human LSC remains undetermined. Here we show that miRNA profiling of fractionated AML populations defines an LSC-specific signature that is highly prognostic for patient survival. Gain- and loss-of-function analyses demonstrated that miR-126 restrained cell cycle progression, prevented differentiation, and increased self-renewal of human LSC. By targeting the G0 to G1 gatekeeper CDK3, miR-126 preserved LSC quiescence and promoted chemotherapy resistance. Thus, in AML, miRNAs influence patient outcome through post-transcriptional regulation of stemness programs in LSC.
HostingRepository	PRIDE
AnnounceDate	2016-03-31
AnnouncementXML	Submission_2016-04-01_17:06:56.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erwin Schoof
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2015-03-30 02:32:25	ID requested
1	2016-03-31 14:17:38	announced
⏵ 2	2016-04-01 17:06:57	announced	Updated publication reference for PubMed record(s): 26832662.

Lechman ER, Gentner B, Ng SW, Schoof EM, van Galen P, Kennedy JA, Nucera S, Ciceri F, Kaufmann KB, Takayama N, Dobson SM, Trotman-Grant A, Krivdova G, Elzinga J, Mitchell A, Nilsson B, Hermans KG, Eppert K, Marke R, Isserlin R, Voisin V, Bader GD, Zandstra PW, Golub TR, Ebert BL, Lu J, Minden M, Wang JC, Naldini L, Dick JE, miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells. Cancer Cell, 29(2):214-28(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: AML, mIR126, global proteomics, SCX, stem cells

John E. Dick
contact affiliation	University Health Network, Princess Margaret Cancer Centre
contact email	jdick@uhnresearch.ca
lab head
Erwin Schoof
contact affiliation	University Health Network
contact email	eschoof@uhnresearch.ca
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/2016/03/PXD001994

PRIDE project URI

• PRIDE
  1. PXD001994
     1. Label: PRIDE project
     2. Name: miR-126 Governs Human Leukemia Stem Cell Quiescence and Therapeutic Resistance