Unknown,Transcriptomics,Genomics,Proteomics

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Comparison of the gene expression profiles of carfilzomib-resistant derivatives versus parental human myeloma cell lines


ABSTRACT: KMS-11 and KMS-34 cells were exposed to stepwise increasing concentrations of carfilzomib over a period of 18 weeks: cells adapted to growth in 4 nM carfilzomib by 4 weeks, in 6 nM in another 6 weeks and in 12 nM after a further 8 weeks. The resulting cell cultures, denoted KMS-11/Cfz and KMS-34/Cfz, respectively, retained resistance to carfilzomib even when tested after removal of selective pressure for approximately 8 weeks. KMS-11/Cfz and KMS-34/Cfz cells were profiled for gene expression after 1 week of growth in the absence of carfilzomib together with parental KMS-11 and KMS-34 cells which had not been selected in the drug (triplicate samples).

ORGANISM(S): Homo sapiens

SUBMITTER: Robert Hawley 

PROVIDER: E-GEOD-69078 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

KLF4-SQSTM1/p62-associated prosurvival autophagy contributes to carfilzomib resistance in multiple myeloma models.

Riz Irene I   Hawley Teresa S TS   Hawley Robert G RG  

Oncotarget 20150601 17


Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such  ...[more]

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