PXD014353

PXD014353 is an original dataset announced via ProteomeXchange.

Title	Carfilzomib-induced reticulocytosis in patients with multiple myeloma is caused by impaired terminal erythroid maturation
Description	Proteasome inhibition constitutes a cornerstone of multiple myeloma (MM) treatment, with bortezomib, carfilzomib and ixazomib approved for clinical use. We observed a consistent and highly significant increase in the reticulocyte count during treatment with carfilzomib-based regimens in patients with relapsed MM, an observation not made in a matched cohort of bortezomib-treated patients. As this increased reticulocytosis was neither associated with elevated hemoglobin levels nor with hemolysis, we subsequently performed in vitro experiments to unravel the underlying mechanisms of this clinical observation. While carfilzomib did not affect erythroid differentiation of CD34+ hematopoietic progenitor cells, both continuous and pulse exposure to carfilzomib significantly impaired terminal maturation of purified primary reticulocytes towards erythrocytes. These results indicate that carfilzomib significantly impairs terminal erythroid maturation, independent of erythroid commitment, expansion or differentiation. Our results report the first pharmacologically induced delay in erythroid maturation as a mechanism for carfilzomib-induced reticulocytosis in MM patients. Quantitative proteomics using LC-MS/MS were performed to assess whether carfilzomib treatment alters the protein composition of reticulocytes
HostingRepository	PRIDE
AnnounceDate	2020-02-20
AnnouncementXML	Submission_2020-02-20_03:29:54.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Delphi Van Haver
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-methionine sulfoxide; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-24 03:57:58	ID requested
⏵ 1	2020-02-20 03:29:55	announced

Kint NG, Heylen E, Pepe D, De Keersmaecker K, Verfaillie CM, Delforge M, Carfilzomib-induced reticulocytosis in patients with multiple myeloma is caused by impaired terminal erythroid maturation. Leukemia, 34(2):651-655(2020) [pubmed]

submitter keyword: Multiple myeloma, carfilzomib, proteasome inhibitors, erythropoiesis

Michel Delforge
contact affiliation	Department of Hematology, University Hospital Leuven, Leuven, Belgium
contact email	Michel.delforge@uzleuven.be
lab head
Delphi Van Haver
contact affiliation	VIB Proteomics Core
contact email	delphi.vanhaver@vib-ugent.be
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/2020/02/PXD014353

PRIDE project URI

• PRIDE
  1. PXD014353
     1. Label: PRIDE project
     2. Name: Carfilzomib-induced reticulocytosis in patients with multiple myeloma is caused by impaired terminal erythroid maturation