Project description:We performed RNA-seq to examine the differences in GC B cells that were either infected with MHV68 or uninfected and between B cells that expressed IgL or IgK B cell receptor light chains.
Project description:We performed single-cell RNA sequencing (scRNA-seq) of intratumoral CD45+ Immune cells from mice subjected to chronic unpredictable mild stress (CUMS) or control conditions. Cells were multiplexed using hashtag oligonucleotides (HTO1-HTO4, TotalSeq-C) and sequenced using the 10x Genomics 5-prime Gene Expression + Feature Barcode + B cell receptor (BCR) V(D)J workflow (Well 3). This dataset contains GEX profiles of intratumoral B cells from 4 samples (2 conditions x 2 biological replicates; 29,456 cells total). BCR V(D)J sequencing data (IGH/IGK/IGL; 1,107 contigs from 604 B cells) from the same tumor well are also provided.
Project description:Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years. To better understand and identify these ‘high-risk’ cases, we analyzed the translocation landscape of myeloma from 795 newly-diagnosed patients by whole genome sequencing from the CoMMpass study. Translocations involving the immunoglobulin lambda (IgL) locus were identified in 10% of patients, and were indicative of poor prognosis. Importantly, 70% of IgL translocations co-occurred with hyperdiploid disease, a marker of standard risk, potentially resulting in the misclassification of IgL-translocated myeloma. Most IgL-translocations coincided with focal amplifications that were centered on the 3’ enhancer. Patients with IgL-translocations failed to benefit from immunomodulatory imide drugs (IMiDs), which target the lymphocyte-specific transcription factor IKZF1 that is bound to the IgL 3’ enhancer at some of the highest levels in the myeloma epigenome. These data implicate IgL-translocation as a driver of poor prognosis which may be due in part to IMID resistance.