PXD006475-1

PXD006475 is an original dataset announced via ProteomeXchange.

Title	Global phosphoproteome analysis of human bone marrow reveals predictive phosphorylation markers for the treatment of acute myeloid leukemia with quizartinib
Description	Treatment with inhibitors of the receptor tyrosine kinase FLT3 are currently studied as promising therapies in acute myeloid leukemia (AML). However, only a subset of patients benefit from these treatments and the presence of activating mutations within FLT3 can predict response to a certain extent only. AC220 (quizartinib) is an example of a potent FLT3 inhibitor1 that was studied in a recent phase II open-label study in patients with relapsed/refractory AML. The complete remission rate (including CRp and CRi) in FLT3-ITD-positive patients was 54% (50/92) and the corresponding partial remission rate (PR) was 17% (16/92)2 Thus, although the FLT3-ITD mutation status correlates with response, the error rate in stratification of patients into responders and non-responders is high, as still 29% of the FLT3-ITD-positive patients failed to respond. Exclusion of FLT3-ITD-negative patients from AC220 treatment also seems critical, as the total response rate (CRþPR) in FLT3-ITD-negative patients is substantially lower (41%, 17/41). As AC220 is a tyrosine kinase inhibitor, we hypothesized that investigating phosphorylation-based signaling on a system-wide scale in AML cells allows for identification of markers enabling more accurate prediction of therapy response as compared to commonly used genetic markers. Hence, we applied quantitative mass spectrometry to decipher a multivariate phosphorylation site marker, which we refer to as phosphosignature, in patient-derived AML blasts that might be useful as predictive biomarkers for AC220 treatment.
HostingRepository	PRIDE
AnnounceDate	2017-05-10
AnnouncementXML	Submission_2017-05-10_02:14:07.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christoph Schaab
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-09 23:46:18	ID requested
⏵ 1	2017-05-10 02:14:08	announced
2	2017-05-15 01:23:58	announced	Updated project metadata.
3	2017-10-24 04:53:16	announced	Updated project metadata.
4	2024-10-22 04:37:19	announced	2024-10-22: Updated project metadata.

Schaab C, Oppermann FS, Klammer M, Pfeifer H, Tebbe A, Oellerich T, Krauter J, Levis M, Perl AE, Daub H, Steffen B, Godl K, Serve H, Global phosphoproteome analysis of human bone marrow reveals predictive phosphorylation markers for the treatment of acute myeloid leukemia with quizartinib. Leukemia, 28(3):716-9(2014) [pubmed]

submitter keyword: biomarker

classification

AML

AC220

quizartinib

phosphoproteomics

response prediction

Christoph Schaab
contact affiliation	Evotec, Martinsried, Germany
contact email	christoph.schaab@evotec.com
lab head
Christoph Schaab
contact affiliation	Evotec
contact email	christoph.schaab@evotec.com
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/2017/05/PXD006475

PRIDE project URI

• PRIDE
  1. PXD006475
     1. Label: PRIDE project
     2. Name: Global phosphoproteome analysis of human bone marrow reveals predictive phosphorylation markers for the treatment of acute myeloid leukemia with quizartinib