Disorders
Myeloma, MGUS, smoldering myeloma, plasmacytoma, Waldenstrom macroglobulinemia: diagnostic thresholds, staging, and what the numbers mean.
2014 revision: added SLiM biomarkers (60% BMPC, FLC ratio 100 or more, MRI focal lesion) to CRAB criteria; changed diagnostic landscape for smoldering myeloma.
Current review of MGUS: diagnostic criteria, risk stratification, progression rates, and management. Light-chain MGUS defined by FLC ratio less than 0.26 or greater than 1.65.
Practical management framework: risk stratification by M-protein level, FLC ratio, and Ig subtype; monitoring intervals by risk tier.
Revised exclusion thresholds for serum FLC ratio; cites IMWG normal range 0.26 to 1.65. Full text verified.
Non-secretory myeloma, non-producing phenotype, presenting as plasma cell leukaemia with plasmablast morphology. Demonstrates that absence of M-protein does not exclude myeloma.
Systematic review with meta-analysis of patients meeting SLiM biomarker criteria; documents outcomes under current treatment paradigms.
Comprehensive review of current and emerging biomarkers (genomic, proteomic, imaging) for detecting MGUS/SMM progression, emphasizing the need for integrated multimodal monitoring.
Develops AI-based risk stratification models integrating genomic, transcriptomic, and clinical data to predict MGUS/SMM progression beyond standard clinical markers.
341 individuals; 5 malignant transcriptional archetypes plus a proliferative program, validated in CoMMpass. FCRL2 nominated as a CAR T target on malignant plasmocytes.
CD20-negative aggressive lymphoma; EBER and MYC rearrangement frequent. Adverse: age 60 or more, advanced stage, high IPI. EPOCH recommended; bortezomib or daratumumab may add.
PYGO2 on 1q21 tracks 1q copy number in CD138-positive plasmocytes; high levels associate with shorter PFS and OS; knockdown raises carfilzomib and bortezomib sensitivity.
MALDI-FT-ICR mass spectrometry imaging on FFPE marrow biopsies; myeloma niches show elevated 3-hydroxykynurenine, rewired tryptophan-kynurenine flux, and increased nucleotide and bioactive lipid metabolism; niche metabolism diverges between MGUS-like marrows and myeloma. Preprint posted Research Square Feb 2026 (PMID 41756448, same study).
Single-cell RNA and BCR sequencing across IgM MGUS, smoldering WM, and symptomatic WM; lower-risk stages harbor multiple B-cell clones where symptomatic WM does not. CD9 and JCHAIN mark the dominant clone, with CD9 preferentially expressed in plasma cell-like tumor cells. MYD88 and IGLL5 mutations found in minor clones. Reinforces that clone size and plasmocyte differentiation pressure distinguish MGUS from overt disease.
Primary plasma cell leukemia (pPCL) is the rarest and most aggressive end of the myeloma spectrum. Retrospective multi-center analysis; randomized trial data are absent and treatment guidance rests on retrospective series. Reports outcomes by consolidation strategy. Outcomes remain poor; illustrates how far the plasmocyte sits from its normal secreting self at the extreme of malignant transformation.