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PXD019725-1

PXD019725 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMetabolic Changes Contribute to Melphalan Resistance in Multiple Myeloma
DescriptionMultiple 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.
HostingRepositoryPRIDE
AnnounceDate2020-07-17
AnnouncementXMLSubmission_2020-07-16_22:50:56.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD019725
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJohn Koomen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListbiotinylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-06-11 16:54:52ID requested
12020-07-16 22:50:56announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Multiple Myeloma, Melphalan, ABPP, Proteomics, LC-MS/MS
Contact List
Ken Shain, MD/PhD
contact affiliationMalignant Hematology Moffitt Cancer Center Tampa, FL, USA
contact emailken.shain@moffitt.org
lab head
John Koomen
contact affiliationMoffitt Cancer Center
contact emailjohn.koomen@moffitt.org
dataset submitter
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Dataset FTP location
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