Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma

Abstract

Multiple myeloma (MM), a plasma cell (PC) malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply scRNA-seq to study the heterogeneity of 40 individuals along MM progression spectrum including 11 healthy controls, demonstrating high interpatient variability that can be explained by expression of known MM drivers and additional putative factors. We identify extensive sub-clonal structures for 10/29 patients. In asymptomatic patients with early disease and in minimal residual disease post-treatment, we detect rare tumor-PC with similar molecular characteristics of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating-tumor-cells (CTC) allows for accurate liquid biopsy and detection of malignant PC, which reflect the patient BM disease. Our work establishes scRNA-seq for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients.

Dissecting intratumor heterogeneity of nodal B cell lymphomas on the transcriptional, genetic, and drug response level

“…Our analysis revealed the coexistence of up to four transcriptionally distinct subpopulations of malignant cells within individual B-NHL lymph node samples. This result recapitulates similar observations in follicular lymphoma [45], multiple myeloma [51] and other cancer entities [8, 12, 52]. We and others attributed this heterogeneity to differentially enriched gene sets, which indicate, for instance, activity of MYC , proliferation, or germinal center experience.…”

Microfluidics as an Enabling Technology for Personalized Cancer Therapy

“…Reverse transcription yields cDNA tagged with the same barcode for mRNA from the same droplet, allowing reads to be assigned back to individual cells after pooled sequencing. The commercially available solution (10x Genomics) has been applied to analyze tumor cells from myeloma patients to reveal the subclonal architecture of tumor cells and allow the post‐therapy characterization of rare residual tumor cells . Furthermore, combining droplet‐based scRNA‐Seq with DNA‐barcoded antibodies allows researchers to assign proteomic information to transcriptomes on the single cell level .…”

Understanding and measuring human B‐cell tolerance and its breakdown in autoimmune disease

“…87 Newer technologies enable investigators to decipher and clone the BCR repertoire of much higher numbers of B-cells and ASC. 89,90,92,93 On the other hand, high-through- ssDNA, dsDNA, insulin, or LPS. 88 The immune repertoire of large numbers of single cells can also be similarly interrogated using automated droplet-based emulsion platforms.…”

“…[89][90][91] The latter approach is able to simultaneously analyze the transcriptional profile of each cell and can therefore categorize the functional phenotype of the cell expressing different BCR. 89,90,92,93 On the other hand, high-through- ssDNA, dsDNA, insulin, or LPS. Some important caveats apply to these assays.…”