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A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis
Julie Støve Bødker1, Rasmus Froberg Brøndum1, Alexander Schmitz1
1Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
Blood Advances
|September 27, 2018
Summary
New B-cell associated gene signatures (BAGS) subtyping improves multiple myeloma (MM) risk stratification. This method identifies subtypes linked to patient survival, offering independent prognostic information beyond current classifications.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Multiple myeloma (MM) remains incurable despite treatment advances.
- Novel risk stratification tools are crucial for optimizing MM therapy.
- Understanding MM heterogeneity is key to personalized treatment.
Purpose of the Study:
- To develop a novel subtyping system for myeloma plasma cells (PCs) using B-cell subset associated gene signatures (BAGS).
- To assess the prognostic impact of BAGS subtypes in multiple myeloma patients.
- To evaluate BAGS as an independent prognostic tool in MM.
Main Methods:
- Combined fluorescence-activated cell sorting and gene expression profiling of normal bone marrow B-cell subsets.
- Generated BAGS for subtyping myeloma PCs from diagnostic samples.
- Analyzed BAGS subtypes in 8 datasets comprising 1772 MM patients, including meta-analysis of 916 patients from 3 trials.
Main Results:
- BAGS subtypes showed consistent frequencies across multiple de novo MM cohorts.
- BAGS subtypes were significantly associated with progression-free and overall survival.
- Pre-BII and memory BAGS subtypes indicated a significantly inferior prognosis.
- BAGS subtypes provided independent prognostic value beyond translocation and cyclin D classification.
Conclusions:
- BAGS subtyping offers a novel approach for risk stratification in multiple myeloma.
- Identified BAGS subtypes have significant prognostic and predictive potential.
- BAGS subtypes highlight the role of acquired B-cell traits and phenotypic plasticity in MM pathogenesis.
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