Project description: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.

2017-04-30 | GSE93984 | GEO

Biochronicity Challenge Study Gene Expression Data

Project description:Biochronicity Challenge Study Gene Expression Data

| PRJNA888385 | ENA

Expression data from Diffuse Large B Cell Lymphoma (DLBCL) patients

Project description:Diffuse large B-cell lymphoma (DLBCL) is currently divided into three main molecular subtypes, defined by gene expression profiling (GEP): Germinal Center B-cell like (GCB), Activated B-Cell like (ABC), and Primary Mediastinal B-cell Lymphoma (PMBL). DLBCL subtypes were determined according to patients' gene expression profiles.

2017-01-30 | GSE87371 | GEO

Development and application of a new immunophenotypic algorithm for molecular subtype classification of Diffuse Large B-Cell Lymphoma (DLBCL): Report from an International DLBCL Rituximab-CHOP Consortium Program Study

Project description:We studied 498 de-novo adult DLBCL cases, which had been diagnosed between January 2002 and October 2009, as part of the International DLBCL Rituximab-CHOP Consortium Program Study We perform global gene expression profiling from formalin fixed paraffin embedded 498 DLBCL tissues RNA by SPIA mediated microarray detection and identified the distinct subgroups of the disease within DLBCL, known as germinal-center-B-cell-like (GCB), activated B-cell-like (ABC), and unclassified DLBCL (UC).

2012-08-01 | GSE31312 | GEO

Molecular subtypes of DLBCL have distinct chromosomal aberrations

Project description:We performed array comparative genomic hybridization (aCGH) and gene expression profiling in 203 samples of diffuse large B cell lymphoma (DLBCL). By gene expression, at least three molecular subtypes of DLBCL termed as germinal center B cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal B cell lymphoma (PMBL) can be distinguished. Combining gene expression profiling and aCGH, revealed copy number abnormalities that had strikingly different frequencies in the three molecular DLBCL subtypes. These data provide genetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways. Keywords: clinical history design The retrospective study included RNA and DNA extracted from 203 clinical samples.

2008-09-04 | E-GEOD-11318 | biostudies-arrayexpress

DLBCL patients

Project description:DLBCL patients

| PRJNA613053 | ENA