Project description:All-trans retinoic acid (ATRA) is important for sensitizing MM cells to carfilzomib (Cfz). To determine what signalling pathways are affected by ATRA in Cfz-treated MM cells, MM.1S MM cell line was pulsed with Cfz and then cultured with DMSO or 10µM ATRA for 12 h. Total RNAs of 2 x 106 MM.1S cells were extracted by RNeasy Mini Kit (Qiagen). 5-10 µg RNA samples were sent to Gene Expression and Genotyping Facility at Case Western Reserve University (Cleveland, OH) for genearray followed by data analysis. We use microarray data to determine differential expression of genes in Cfz-treated MM cells in culture with DMSO and ATRA.
Project description:ATRA is important for sensitizing MM cells to Cfz. To determine what signalling pathways are affected by ATRA+Cfz in MM cells, MM.1S MM cell line was pulsed with Cfz and then cultured with DMSO or 10µM ATRA for 12 h. Total RNAs of 2 x 106 MM.1S cells for each sample were extracted by RNeasy Mini Kit (Qiagen). 5-10 µg RNA samples were sent to Cancer Genomics Center at The University of Texas (Houston, TX) for genearray followed by data analysis. We use gene experssion profiling data to determine differential expression of genes in MM cells in culture with DMSO, ATRA, Cfz or ATRA+Cfz.
Project description:The multiple myeloma (MM) data set (endpoints F, G, H, and I) was contributed by the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences (UAMS, Little Rock, AR, USA). Gene expression profiling of highly purified bone marrow plasma cells was performed in newly diagnosed patients with MM. The training set consisted of 340 cases enrolled on total therapy 2 (TT2) and the validation set comprised 214 patients enrolled in total therapy 3 (TT3). Plasma cells were enriched by anti-CD138 immunomagnetic bead selection of mononuclear cell fractions of bone marrow aspirates in a central laboratory. All samples applied to the microarray contained more than 85% plasma cells as determined by 2-color flow cytometry (CD38+ and CD45-/dim) performed after selection. Dichotomized overall survival (OS) and eventfree survival (EFS) were determined based on a two-year milestone cutoff. A gene expression model of high-risk multiple myeloma was developed and validated by the data provider and later on validated in three additional independent data sets.
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.
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.
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.
Project description:Purpose: We report the NGS-derived transcriptome profiling (paired-end RNA-seq) following proteasome inhibition in the multiple myeloma cell line MM.1S. Methods: MM.1S cells were treated for six hours with the synthetic proteasome inhibitor lactacystin or clinically-approved proteasome inhibitor bortezomib and RNA expression changes were quantified and compared to DMSO control-treated cells by RNA-sequencing.
Project description:Most patients with multiple myeloma (MM) will eventually relapse and current treatments have limited effect. Herein, we demonstrate that succinate dehydrogenase subunitA (SDHA) was low expressed in MM patients, and patients with SDHA relatively high expression had long overall survival and progression-free survival. Furthermore, SDHA high expression inhibited proliferation and invasion in multiple myeloma (MM) cell lines and enhanced the anti-tumor and synergistic effect of chemotherapeutics. We conducted transcriptome comparison of BMMCs of three MM patients treated with DMSO or chidamide.