Perturbed ER homeostasis in primary amyloidogenic PCs. Assessment of ER abundance and homeostasis in primary PCs by EM (5-35 PCs per patient; 7 AL, 5 MM, and 3 MGUS patients per group) and G6Pase EM cytochemistry (>20 PCs per patient; 3 AL, 3 MM patients per group). (A) Representative EM images of BM PCs in AL, MM, and MGUS patients (insets: magnification ×1840), and quantification of ER size by stereography counting the number of ER cisternae intersecting the main cellular axes. Box plots show median, maximum, and minimum, and first and third quartile values. (B) Representative G6Pase EM cytochemistry images of BM PCs in AL and MM patients, and automated quantification of G6Pase⁺ area (ER size), relative to total cell area (mean ± standard error). (C) Quantitative reverse transcription PCR analysis of transcripts encoding ER-stress responsive proteins (8 AL and 7 MM primary samples). Histograms show mean values ± standard error. ***P < .0001; *P < .05 (Student t test). BiP, immunoglobulin heavy chain binding protein; CHOP, CCAAT/enhancer-binding protein homologous protein; sXBP1, spliced X-box binding protein 1; tXBP1, total X-box binding protein 1.