Functional gene expression analysis of clonal plasma cells identifies a unique molecular profile for light chain amyloidosis.
Immunoglobulin light chain amyloidosis (AL) is characterized by a clonal expansion of plasma cells within the bone marrow. Gene expression analysis was used to identify a unique molecular profile for AL using enriched plasma cells (CD138+) from the bone marrow of 24 patients with AL and 28 patients with multiple myeloma (MM) and 6 healthy controls. Class prediction analysis (PAM) revealed a subset of 12 genes, which included TNFRSF7 (CD27), SDF-1, and PSMA2, that distinguished between these 2 groups with an estimated and observed accuracy of classification of 92%. This model was validated with an independent dataset of 11 patients with AL and 12 patients with MM with 87% accuracy. Differential expression for the most discriminant genes in the 12-gene subset was validated using quantitative real-time polymerase chain reaction and protein expression analysis, which upheld the observations from the micro-array expression data. Functional analyses using a novel network mapping software revealed a number of potentially significant pathways that were dysregulated in patients with AL, with those regulating proliferation, apoptosis, cell signaling, chemotaxis, and migration being substantially represented. This study provides new insight into the molecular profile of clonal plasma cells and its functional relevance in the pathogenesis of light chain amyloidosis.
Abraham
Roshini S
RS
Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. abraham.roshini@mayo.edu
Ballman
Karla V
KV
Dispenzieri
Angela
A
Grill
Diane E
DE
Manske
Michelle K
MK
Price-Troska
Tammy L
TL
Paz
Natalia Gonzalez
NG
Gertz
Morie A
MA
Fonseca
Rafael
R
D000368:Aged; D000686:Amyloidosis / Q000175:diagnosis / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D002999:Clone Cells; D019938:Cyclin D1 / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling / Q000592:standards; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics*; D010950:Plasma Cells / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016160:Retinoblastoma Protein / Q000235:genetics; D014178:Translocation, Genetic
D007147:Immunoglobulin Light Chains; D016160:Retinoblastoma Protein; D019938:Cyclin D1