Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The IL6Myc mouse is an immunocompetent model for the development of aggressive multiple myeloma (MM) [tumor RNA-seq]

ABSTRACT: Multiple Myeloma (MM) is a neoplasm of plasma cells originating in the bone marrow and is the second most common blood cancer in the United States. One challenge in understanding the pathogenesis of Multiple Myeloma (MM) and improving treatment is a lack of immunocompetent mouse models. We previously developed the IL6Myc mouse that generates plasmacytomas at 100% frequency that phenotypically resemble aggressive MM. Using comprehensive genomic analysis, we found that the RNA expression patterns between tumors were somewhat heterogenous, but nonetheless resembled MMSET (multiple myeloma SET domain), an aggressive form of human myeloma with poor prognosis. Cell lines derived from the mouse tumors expressed cell-surface markers typical of MM, but also expressed BAFF-R, which is infrequently found in human MM. The cell lines also had heterogeneous responses to chemotherapeutic drugs typically used to treat human MM. Interestingly IL6Myc tumors accumulated variants in genes like those seen in human MM, as well as recurrent Ig translocations, a common characteristic of human MM. These data indicate that the IL6Myc model is a useful model for aggressive MM that can be used to develop treatment and understand how early myc expression influences disease etiology.

ORGANISM(S): Mus musculus

PROVIDER: GSE220825 | GEO | 2023/12/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The IL6Myc mouse is an immunocompetent model for the development of aggressive multiple myeloma (MM) [WES]

Project description:Multiple Myeloma (MM) is a neoplasm of plasma cells originating in the bone marrow and is the second most common blood cancer in the United States. One challenge in understanding the pathogenesis of Multiple Myeloma (MM) and improving treatment is a lack of immunocompetent mouse models. We previously developed the IL6Myc mouse that generates plasmacytomas at 100% frequency that phenotypically resemble aggressive MM. Using comprehensive genomic analysis, we found that the RNA expression patterns between tumors were somewhat heterogenous, but nonetheless resembled MMSET (multiple myeloma SET domain), an aggressive form of human myeloma with poor prognosis. Cell lines derived from the mouse tumors expressed cell-surface markers typical of MM, but also expressed BAFF-R, which is infrequently found in human MM. The cell lines also had heterogeneous responses to chemotherapeutic drugs typically used to treat human MM. Interestingly IL6Myc tumors accumulated variants in genes like those seen in human MM, as well as recurrent Ig translocations, a common characteristic of human MM. These data indicate that the IL6Myc model is a useful model for aggressive MM that can be used to develop treatment and understand how early myc expression influences disease etiology.

2023-12-06 | GSE220827 | GEO

The IL6Myc mouse is an immunocompetent model for the development of aggressive multiple myeloma (MM) [cell line RNA-seq]

2023-12-06 | GSE220823 | GEO

Effects of MMSET on gene expression in multiple myeloma

Project description:The MMSET (Multiple Myeloma SET domain) protein is overexpressed in multiple myeloma patients with the translocation t(4;14). Although studies have shown the involvement of MMSET/WHSC1 in development, its mode of action in the pathogenesis of multiple myeloma (MM) is largely unknown. We found that MMSET is a major regulator of chromatin structure and transcription in t(4;14) MM cells. High levels of MMSET correlate with an increase in lysine 36 methylation of histone H3 and a decrease in lysine 27 methylation across the genome, leading to a more open structural state of the chromatin. Loss of MMSET expression alters adhesion properties, suppresses growth and induces apoptosis in MM cells. Consequently, genes affected by high levels of MMSET are implicated in the p53 pathway, cell cycle regulation and integrin signaling. Regulation of many of these genes required functional histone methyl-transferase (HMT) activity of MMSET. These results implicate MMSET as a major epigenetic regulator in t(4;14)+ MM.

2010-10-20 | GSE24746 | GEO

MMSET regulates transcription factors critical for survival of t(4;14) myeloma myeloma cells

2014-07-16 | GSE59424 | GEO

MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple myeloma cells

Project description:Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. The translocation t(4;14)(p16;q32) is one of the most common translocation in MMs, affecting 15% of patients, and is associated with very poor prognosis. The histone methyltransferase (HMTase) MMSET is universally overexpressed in t(4;14) MM as a result of the t(4;14) translocation. MMSET is capable of producing 3 major isoforms, the full length MMSET II, short isoforms REIIBP and MMSET I. MMSET II has been suggested to play an important tumorigenic role in t(4;14) MM, but little is yet known about whether and how the MMSET short isoforms contribute to MM tumorigenesis. The aim of this study is to characterize MMSET I roles and determine its downstream targets in t(4;14) MM. In t(4;14) MM cells MMSET I knockdown with shRNAs induced cell apoptosis, reduced colony formation and inhibited tumorigenicity in vivo. We also found MMSET I knockdown decreased GLO1 expression, and ectopic MMSET I increased GLO1 expression, suggesting that MMSET I is an upstream regulator of GLO1. Further analysis indicated that MMSET I bound to GLO1 promoter region and depended on its C-terminus to regulate GLO1 expression. Our preliminary data suggested that MMSET I is an oncoprotein and could regulate GLO1 expression in t(4;14) multiple myeloma cells.

2019-01-01 | GSE98433 | GEO

Effects of MMSET on gene expression in multiple myeloma

2010-10-20 | E-GEOD-24746 | biostudies-arrayexpress

MMSET regulates transcription factors critical for survival of t(4;14) myeloma myeloma cells

Project description:Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. The multiple myeloma SET domain (MMSET), identified by its fusion to the IgH locus in t(4;14) MM, is universally overexpressed and has been suggested to play an important role in tumorigenicity in t(4;14) MM. In order to identify downstream functional targets of MMSET, we knocked down MMSET expression with shRNAs in KMS11, a t(4;14) MM cell line, and identified differentially expressed genes by gene expression microarray analysis. KMS11 cells were treated with shRNAs for 48 h. Total RNA was extracted by using the Qiagen RNeasy Mini kit (Germany). Gene expression was performed using the GeneChip Human Genome U133A Array (Affymetrix) following the manufacturerM-bM-^@M-^Ys instructions. Data analysis was performed using GeneSpring software from Agilent Technologies.

2014-07-16 | E-GEOD-59424 | biostudies-arrayexpress

Epigenetic modifiers MMSET and EZH2 physically interact and cooperate to support Multiple Myeloma pathophysiology [ChIP-seq]

Project description:Multiple myeloma (MM) is a malignant B cell dyscrasia characterized by the accumulation of clonal plasma cells (PC) within the bone marrow. Epigenetic factors are involved in MM initiation, progression, and occurrence of chemoresistance. Among them EZH2, the Polycomb Repressive Complex 2 (PRC2) catalytic subunit and NSD2 (MMSET), the target oncogene of t(4;14) primary translocation, are both associated with poor prognosis values and contribute to MM disease. In this study, we identified a physical interaction between EZH2 and MMSET in MM. We used MMSET-depleted MM cells and MAK-683, an allosteric inhibitor of EZH2, to disrupt this interaction and understand its implication in MM biology and resistance to anti-MM drugs. Through its interaction with EZH2, MMSET regulates PRC2 nuclear localization in MM cells, promotes a particularly poor prognosis in MM patients, and modulates the expression of tumor-suppressor genes involved in p53 pathway. We also demonstrated that MAK-683 can interfere with this interaction and synergizes with conventional drugs used in MM treatment: Melphalan, an alkylating agent triggering DNA Damage Response (DDR); and Panobinostat, a Histone De-Acetylase (HDAC) inhibitor directedly regulating p53 acetylation and stability.

2024-08-09 | GSE242500 | GEO

Epigenetic modifiers MMSET and EZH2 physically interact and cooperate to support Multiple Myeloma pathophysiology [RNA-seq]

2024-08-09 | GSE242451 | GEO

The IL6Myc mouse is an immunocompetent model for the development of aggressive multiple myeloma (MM)

Project description:The IL6Myc mouse is an immunocompetent model for the development of aggressive multiple myeloma (MM)

| PRJNA911669 | ENA