Publications by authors named "Davine Hofste op Bruinink"
Article Synopsis
- The study analyzed genomic and transcriptomic changes in 29 multiple myeloma patients pre- and post-treatment, revealing that 82% showed changes in clonal composition and a rise in single-nucleotide variants (SNVs) from 67 to 86.
- Notable increases in genetic abnormalities were observed in RAS genes, amp1q21, and TP53, with a specific mutation signature found regardless of melphalan dosage.
- Differential gene expression analysis showed significant pathway changes linked to increased proliferation and metabolism in late-stage disease, highlighting several potentially targetable genes.
Purpose: Primary plasma cell leukemia (pPCL) is an aggressive subtype of multiple myeloma, which is distinguished from newly diagnosed multiple myeloma (NDMM) on the basis of the presence of ≥ 20% circulating tumor cells (CTCs). A molecular marker for pPCL is currently lacking, which could help identify NDMM patients with high-risk PCL-like disease, despite not having been recognized as such clinically.
Methods: A transcriptomic classifier for PCL-like disease was bioinformatically constructed and validated by leveraging information on baseline CTC levels, tumor burden, and tumor transcriptomics from 154 patients with NDMM included in the Cassiopeia or HO143 trials and 29 patients with pPCL from the EMN12/HO129 trial.
Longitudinal minimal residual disease assessment in multiple myeloma patients in complete remission - results from the NMSG flow-MRD substudy within the EMN02/HO95 MM trial.
BMC Cancer
February 2022
Background: Multiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treatment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. However, for multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation.
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- Minimal residual disease (MRD) assessment using multiparameter flow cytometry (MFC) is a key method for determining treatment effectiveness in newly diagnosed multiple myeloma (MM) patients.
- In a study of 321 patients, 76% were found to be MRD-negative at enrollment, with MRD-negative patients showing significantly better 5-year progression-free survival (66% vs. 31%) and overall survival (86% vs. 69%) compared to MRD-positive patients.
- The study also found that lenalidomide maintenance treatment increased the rate of patients transitioning from MRD-positive to MRD-negative after one year.
Progression and persistence of malignancies are influenced by the local tumor microenvironment, and future eradication of currently incurable tumors will, in part, hinge on our understanding of malignant cell biology in the context of their nourishing surroundings. Here, we generated paired single-cell transcriptomic datasets of tumor cells and the bone marrow immune and stromal microenvironment in multiple myeloma. These analyses identified myeloma-specific inflammatory mesenchymal stromal cells, which spatially colocalized with tumor cells and immune cells and transcribed genes involved in tumor survival and immune modulation.
View Article and Find Full Text PDFMinimal residual disease (MRD) tracking, by next generation sequencing of immunoglobulin sequences, is moving towards clinical implementation in multiple myeloma. However, there is only sparse information available to address whether clonal sequences remain stable for tracking over time, and to what extent light chain sequences are sufficiently unique for tracking. Here, we analyzed immunoglobulin repertoires from 905 plasma cell myeloma and healthy control samples, focusing on the third complementarity determining region (CDR3).
View Article and Find Full Text PDFPurpose: The IGF and mTOR-pathways are considered as potential targets for therapy in patients with adrenocortical carcinoma (ACC). This study aims to describe the IGF pathway in ACC and to explore the response to the combined treatment with the IGF1R/IR inhibitor linsitinib, and mTOR inhibitors (sirolimus and everolimus) in in vitro models of ACC.
Methods: The protein expression level of IGF2, IGF1R and IGF2R was evaluated by immunohistochemistry in 17 human ACCs and the mRNA expression level of IGF1, IGF2, IGF1R, IR isoforms A and B, IGF2R, IGF-Binding-Proteins[IGFBP]-1, 2, 3 and 6 was evaluated by RT-qPCR in 12 samples.