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Series GSE93984 Query DataSets for GSE93984
Status Public on Apr 30, 2017
Title Expression data from DLBCL tumor biopsies
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton’s tyrosine kinase (BTK)–mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and FL lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy.
 
Overall design Gene expression in ibrutinib pretreated tumor biopsy samples from ABC-DLBCL patients was detected by U133 plus 2.0 arrays and the correlation of BCL2 expression and patient response to ibrutinib or PFS after ibrutinib treatment was analyzed. There are total 28 ABC-DLBCL samples. 17 of them are non-responders (PD+SD) and 11 of them are responders (PR+CR). For this analysis restricted to ABC-DLBCL subtype, only the ABC-DLBCL samples were used and normalized separately.

Data was processed with all subsets of DLBCL samples (60 samples) and also separately for 28 ABC-DLBCL samples ('re-analysis' samples).

The values in the sample 'characteristics' field represent:
response:
CR=complete response, PR=partial response, SD=stable disease, PD=progression disease
class:
NR=non-responder, RR=responder
subtype:
ABC=ABC-DLBCL, GCB=GCB-DLBCL, UNC=unclassified subtype
progression_free_survival_censor:
censored case = 1; event (death/progression) = 0 in the censoring variable for the progression free survival analysis
 
Contributor(s) Kuo H, Ezell SA, Schweighofer KJ, Cheung LW, Hsieh S, Apatira M, Sirisawad M, Eckert K, Hsu J, Chen C, Beaupre D, Versele M, Chang BY
Citation(s) 28428442
Submission date Jan 24, 2017
Last update date Mar 25, 2019
Contact name Hsu-Ping Kuo
E-mail(s) [email protected]
Phone 4082153739
Organization name Pharmacyclics
Street address 995 E Arques Ave
City Sunnyvale
State/province CA
ZIP/Postal code 94087
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (88)
GSM2466052 FFPE embedded lymph node at baseline [AA_SNSA_madbID119985]
GSM2466053 FFPE embedded lymph node at baseline [AB_SNSA_madbID119987]
GSM2466054 FFPE embedded lymph node at baseline [AC_SNSA_madbID119988]
This SubSeries is part of SuperSeries:
GSE93986 Expression data from DLBCL tumor biopsies and TMD8 cell line
Relations
BioProject PRJNA363010

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE93984_RAW.tar 429.9 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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