PXD019725-1

PXD019725 is an original dataset announced via ProteomeXchange.

Title	Metabolic Changes Contribute to Melphalan Resistance in Multiple Myeloma
Description	Multiple myeloma is an incurable hematological malignancy that impacts tens of thousands of people every year in the U.S. Treatment for eligible patients includes three stages: induction, consolidation with stem cell rescue, and maintenance. High dose therapy with the DNA alkylating agent, melphalan, remains the primary drug for consolidation therapy in conjunction with autologous stem cell transplant. As a result, melphalan resistance remains a clinical challenge. Here, we use proteometabolomics to examine mechanisms of melphalan resistance in two cell line models. Drug metabolism, steady-state metabolomics, activity-based protein profiling (ABPP), acute treatment metabolomics, and immunoblotting analyses have allowed us to further elucidate metabolic processes contributing to melphalan resistance. Proteometabolomics data indicate that both drug resistant cells have higher levels of pentose phosphate pathway metabolites than their naïve counterparts. Interestingly, we also observed cell line specific changes in purine, pyrimidine and glutathione metabolism that are linked to the differences in steady state metabolism of naïve cells and highlight the heterogeneity of melphalan resistance in these models. Because of the diversity of metabolic changes, our data suggest that omics approaches will be needed to fully examine melphalan resistance in patient specimens and define personalized strategies to optimize the delivery of this therapy.
HostingRepository	PRIDE
AnnounceDate	2020-07-17
AnnouncementXML	Submission_2020-07-16_22:50:56.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD019725
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-11 16:54:52	ID requested
⏵ 1	2020-07-16 22:50:56	announced

Dataset with its publication pending

submitter keyword: Multiple Myeloma, Melphalan, ABPP, Proteomics, LC-MS/MS

Ken Shain, MD/PhD
contact affiliation	Malignant Hematology Moffitt Cancer Center Tampa, FL, USA
contact email	ken.shain@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019725
     1. Label: PRIDE project
     2. Name: Metabolic Changes Contribute to Melphalan Resistance in Multiple Myeloma