GSE153627 Single-cell RNAseq of VQ myeloma cells reveals unique transcriptional signatures from normal plasma cells

Contributors : Adhithi Rajagopalan ; Zhi Wen ; Robert Burns ; Jing ZhangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusNRAS Q61 mutations are prevalent in advanced/relapsed multiple myeloma (MM) and correlate with poor patient outcomes. Thus, we generated a novel MM model by conditionally activating expression of endogenous NrasQ61R and a MYC transgene in germinal center B cells (VQ mice). VQ mice developed a highly malignant MM characterized by high proliferation index, hyperactivation of ERK and AKT signaling, impaired hematopoiesis, widespread extramedullary disease, bone lesions, kidney abnormalities, preserved PD1 and TIGIT immune checkpoint pathways, and expression of human high-risk MM gene signatures. VQ MM mice recapitulate most of the biological and clinical features of human advanced/high-risk MM. These MM phenotypes are serially transplantable in syngeneic recipients. Two MM cell lines were also derived to facilitate future genetic manipulations. Combination therapies based on MEK inhibition significantly prolonged the survival of VQ mice with advanced stage MM. Our study provides a strong rationale to develop MEK inhibition-based therapies for treating advanced/relapsed MM.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research