Functional gene expression analysis of clonal plasma cells identifies a unique molecular profile for light chain amyloidosis

Roshini S. Abraham, Karla V. Ballman, Angela Dispenzieri, Diane E. Grill, Michelle K. Manske, Tammy L. Price-Troska, Natalia Gonzalez Paz, Morie Gertz, Rafael Fonseca

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)794-803
Number of pages10
JournalBlood
Volume105
Issue number2
DOIs
StatePublished - Jan 15 2005

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Amyloidosis
Plasma Cells
Gene expression
Genes
Plasmas
Gene Expression
Light
Bone
Cell signaling
Immunoglobulin Light Chains
Pulse amplitude modulation
Polymerase chain reaction
Set theory
Multiple Myeloma
Bone Marrow
Apoptosis
Chemotaxis
Real-Time Polymerase Chain Reaction
Proteins
Software

ASJC Scopus subject areas

  • Hematology

Cite this

Functional gene expression analysis of clonal plasma cells identifies a unique molecular profile for light chain amyloidosis. / Abraham, Roshini S.; Ballman, Karla V.; Dispenzieri, Angela; Grill, Diane E.; Manske, Michelle K.; Price-Troska, Tammy L.; Paz, Natalia Gonzalez; Gertz, Morie; Fonseca, Rafael.

In: Blood, Vol. 105, No. 2, 15.01.2005, p. 794-803.

Research output: Contribution to journalArticle

Abraham, Roshini S. ; Ballman, Karla V. ; Dispenzieri, Angela ; Grill, Diane E. ; Manske, Michelle K. ; Price-Troska, Tammy L. ; Paz, Natalia Gonzalez ; Gertz, Morie ; Fonseca, Rafael. / Functional gene expression analysis of clonal plasma cells identifies a unique molecular profile for light chain amyloidosis. In: Blood. 2005 ; Vol. 105, No. 2. pp. 794-803.
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abstract = "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.",
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