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Cell growth in aggregates determines gene expression, proliferation, survival and chemoresistance of Follicular Lymphoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE41856 | GEO | 2012/10/27

SECONDARY ACCESSION(S): PRJNA178327

REPOSITORIES: GEO

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Cell growth in aggregates determines gene expression, proliferation, survival and chemoresistance of Follicular Lymphoma

Project description:This SuperSeries is composed of the following subset Series: GSE41851: Expression data from follicular lymphoma cells cultured either in suspension either as Multicellular aggregates of lymphoma cells (MALC) GSE41855: Expression data from quiescent cells and cycling cells isolated from Multicellular aggregates of lymphoma cells (MALC) Refer to individual Series

2012-10-27 | E-GEOD-41856 | biostudies-arrayexpress

Cell growth in aggregates determines gene expression, proliferation, survival and chemoresistance of Follicular Lymphoma

Project description:Cell growth in aggregates determines gene expression, proliferation, survival and chemoresistance of Follicular Lymphoma

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Inherited genetic variation and overall survival following follicular lymphoma.

Project description:Follicular lymphoma (FL) has variable progression and survival, and improved identification of patients at high risk for progression would aid in identifying patients most likely to benefit from alternative therapy.In a sample of 244 FL cases identified during a population-based case-control study of non-Hodgkin lymphoma (NHL), we examined 6,679 tag SNPs in 488 gene regions for associations with overall FL survival. Over a median follow-up of 89 months with 65 deaths in this preliminary study, we identified 5 gene regions (BMP7, GALNT12,DUSP2, GADD45B, and ADAM17) that were associated with overall survival from FL. Results did not meet the criteria for statistical significance after adjustment for multiple hypothesis testing. These results,which support a role for host factors in determining the variable progression of FL, serve as an initial examination that can inform future studies of genetic variation and FL survival. However, they require replication in independent populations, as well as assessment in rituximab-treated patients.

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Disparities in survival by insurance status in follicular lymphoma.

Project description:Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma and most common indolent non-Hodgkin lymphoma. Lower socioeconomic status is associated with poor outcomes in FL, suggesting that access to care is an important prognostic factor; however, the association between insurance status and FL survival has not been sufficiently examined. The National Cancer Database, a nationwide cancer registry, was used to evaluate 43?648 patients with FL diagnosed between 2004 and 2014. All analyses were performed on 2 cohorts segmented at age 65 years to account for changes in insurance status with Medicare eligibility. Cox proportional hazard models calculated hazard ratios (HRs) with confidence intervals (CIs) for the association between insurance status and overall survival (OS) controlling for the available sociodemographic and prognostic factors. Kaplan-Meier curves display outcomes by insurance status for patients covered by private insurance, no insurance, Medicaid, or Medicare. When compared with patients younger than age 65 years with private insurance, patients younger than age 65 years with no insurance (HR, 1.96; 95% CI, 1.69-2.28), with Medicaid (HR, 1.82; 95% CI, 1.57-2.12), and with Medicare (HR, 1.96; 95% CI, 1.71-2.24) had significantly worse OS after adjusting for sociodemographic and prognostic factors. Compared with patients age 65 years or older with private insurance, those with Medicare only (HR, 1.28; 95% CI, 1.17-1.4) had significantly worse OS. For adults with FL, expanding access to care through insurance has the potential to improve outcomes.

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BCL6 Antagonizes NOTCH2 to Maintain Survival of Human Follicular Lymphoma Cells.

Project description:Although the BCL6 transcriptional repressor is frequently expressed in human follicular lymphomas (FL), its biological role in this disease remains unknown. Herein, we comprehensively identify the set of gene promoters directly targeted by BCL6 in primary human FLs. We noted that BCL6 binds and represses NOTCH2 and NOTCH pathway genes. Moreover, BCL6 and NOTCH2 pathway gene expression is inversely correlated in FL. Notably, BCL6 upregulation is associated with repression of NOTCH2 and its target genes in primary human and murine germinal center (GC) cells. Repression of NOTCH2 is an essential function of BCL6 in FL and GC B cells because inducible expression of Notch2 abrogated GC formation in mice and killed FL cells. Indeed, BCL6-targeting compounds or gene silencing leads to the induction of NOTCH2 activity and compromises survival of FL cells, whereas NOTCH2 depletion or pathway antagonists rescue FL cells from such effects. Moreover, BCL6 inhibitors induced NOTCH2 expression and suppressed growth of human FL xenografts in vivo and primary human FL specimens ex vivo These studies suggest that established FLs are thus dependent on BCL6 through its suppression of NOTCH2Significance: We show that human FLs are dependent on BCL6, and primary human FLs can be killed using specific BCL6 inhibitors. Integrative genomics and functional studies of BCL6 in primary FL cells point toward a novel mechanism whereby BCL6 repression of NOTCH2 drives the survival and growth of FL cells as well as GC B cells, which are the FL cell of origin. Cancer Discov; 7(5); 506-21. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 443.

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Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival.

Project description:Recent gene-expression data have suggested that host immune genetic signatures may predict outcomes in patients with follicular lymphoma. We evaluated the hypothesis that germ line common variation in candidate immune genes is associated with survival. Cox models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for individual SNPs after accounting for age, clinical, and other demographic factors. The median age at diagnosis of the 278 patients was 57 years, and 59 (21%) of the patients died during follow-up, with a median follow-up of 59 months (range, 27-78 months) for surviving patients. SNPs in IL8 (rs4073; HR(TT)=2.14, 1.26-3.63), IL2 (rs2069762; HR(GT/TT) = 1.80, 1.06-3.05), IL12B (rs3212227; HR(AC/CC)=1.83, 1.06-3.06), and IL1RN (rs454078; HR(AA)=1.93, 1.11-3.34) were the most robust predictors of survival. A summary score of the number of deleterious genotypes from these genes was strongly associated with survival (P=.001). A risk score that combined the 4 SNPs with the clinical and demographic factors was even more strongly associated with survival (P<.001); the 5-year Kaplan-Meier survival estimates were 96% (93%-100%), 72% (62%-83%), and 58% (48%-72%) for groups at low, intermediate, and high risk, respectively. Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma.

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Overlap Between Pediatric Nodal Marginal Zone Lymphoma (PNMZL) and Pediatric-Type Follicular Lymphoma (PTFL) : Morphological and Molecular Analysis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-11 | GSE154834 | GEO