Vacuolated Marrow Cytopenias from Copper Deficiency to UBA1-Mutant VEXAS: Molecular Landscape, Systematic Review, and Cost-Efficient Diagnostic Algorithm

source extracted confidence: high 2026-04-09
#humans #algorithms #bone-marrow #copper #cost-benefit-analysis

Vacuolated Marrow Cytopenias from Copper Deficiency to UBA1-Mutant VEXAS: Molecular Landscape, Systematic Review, and Cost-Efficient Diagnostic Algorithm

Takami et al., 2025 | Int J Mol Sci | Systematic Review

Citation

Takami Akiyoshi, Uchino Kaori, ... Enomoto Megumi. Vacuolated Marrow Cytopenias from Copper Deficiency to UBA1-Mutant VEXAS: Molecular Landscape, Systematic Review, and Cost-Efficient Diagnostic Algorithm. Int J Mol Sci. 2025-Aug-20;26(16). doi:10.3390/ijms26168044

Abstract

Although cytoplasmic vacuoles are instantly recognizable on bone marrow smears, their etiologic significance remains a diagnostic dilemma in everyday practice. We conducted a PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) aligned systematic review with narrative synthesis registered in PROSPERO and refrained from meta-analysis owing to high between-study heterogeneity (I2 > 80%). Across 22 studies, we identified 818 unique adults with vacuolated marrow cytopenias. A stepwise diagnostic algorithm-serum copper/ceruloplasmin followed, when non-diagnostic, by UBA1 hotspot sequencing in adults meeting clinical "red flags"-correctly classified 97% of cases within <5 days at a median laboratory cost of ~USD 173, reserving broad myeloid next-generation sequencing for the atypical minority. This synthesis clarifies the relative frequency of major etiologies and provides a cost-efficient, practice-ready pathway that bridges trace-metal metabolism and somatic genomics.

Key Findings

This synthesis clarifies the relative frequency of major etiologies and provides a cost-efficient, practice-ready pathway that bridges trace-metal metabolism and somatic genomics.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 22
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Algorithms
  • Bone Marrow
  • Copper
  • Cost-Benefit Analysis
  • Cytopenia
  • Mutation
  • Ubiquitin-Activating Enzymes
  • Myelodysplastic Syndromes
  • Skin Diseases, Genetic

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: copper

Provenance

Source extracted via PubMed E-utilities API on 2026-04-10