PXD027594

PXD027594 is an original dataset announced via ProteomeXchange.

Title	Functional multi-omics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma
Description	CD38 is a surface ectoenzyme expressed at high levels on myeloma plasma cells and is the target for the monoclonal antibodies (mAbs) daratumumab and isatuximab. CD38 density on tumor cells is an important determinant of mAb efficacy while CD38 is lost after mAb treatment. Several small molecules have been found to increase tumor surface CD38, with the goal of boosting mAb efficacy in a co-treatment strategy. Here we sought to extend our currently limited insight into CD38 surface expression by using a multi-omics approach. Genome-wide CRISPR-interference screens integrated with patient-centered epigenetic analysis confirmed known regulators of CD38, such as RARA, while revealing XBP1 and SPI1 as other key transcription factors governing surface CD38 levels. CD38 knockdown followed by cell surface proteomics demonstrated no significant remodeling of the myeloma “surfaceome” after genetically-induced loss of this antigen. Integrated transcriptome and surface proteome data confirmed high specificity of all-trans retinoic acid in upregulating CD38 in contrast to broader effects of azacytidine and panobinostat. Finally, unbiased phosphoproteomics identified inhibition of MAP kinase pathway signaling in tumor cells after daratumumab treatment. Our work provides a resource to design strategies to enhance efficacy of CD38-targeting immunotherapies in myeloma.
HostingRepository	PRIDE
AnnounceDate	2021-07-29
AnnouncementXML	Submission_2021-07-28_23:49:14.499.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Neha Paranjape
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-27 07:27:24	ID requested
⏵ 1	2021-07-28 23:49:14	announced

Dataset with its publication pending

submitter keyword: CD38, ATRA, daratumamab, azacytidine, panobinostat, CRISPR-interference, myeloma surfaceome, phosphoproteomics

ARUN PAUL WIITA
contact affiliation	Department of Laboratory Medicine, University of California, San Francisco, USA
contact email	arun.wiita@ucsf.edu
lab head
Neha Paranjape
contact affiliation	University of California, San Francisco
contact email	paranjape.neha@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027594
     1. Label: PRIDE project
     2. Name: Functional multi-omics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma