What question did this study set out to answer?

Identify biomarkers and therapeutic targets in plasma cell disorders related to proteostasis and amyloidosis.

December 8, 2025Blood

Aberrant clonal plasma cells bypass the proteasome proteostasis by endoplasmic reticulum associated protein degradation

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This research reveals unique biomarkers and pathways in proteostasis of plasma cells affected by amyloidosis, indicating novel therapeutic targets.

Identify biomarkers and therapeutic targets in plasma cell disorders related to proteostasis and amyloidosis.
Next-generation RNA sequencing of bone marrow aspirates from 84 treatment-naïve plasma cell disorder patients.
Differential expression analysis using tximport/edgeR and variant calling in mRNA.
Analysis of mutation and expression data to identify unique profiles for AL compared to MM and MGUS.
Dysregulated proteostasis and unique mutational signatures in AL compared to MM and MGUS were identified.
ER stress and unfolded protein response pathways were shown to correlate with increasing plasma cell burden.
Potential early-stage biomarkers linked specifically to AL were observed, which may aid in earlier diagnosis.

O’Donnell et al. (2025) studied this question.

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This research reveals unique biomarkers and pathways in proteostasis of plasma cells affected by amyloidosis, indicating novel therapeutic targets.