Calreticulin expression in the clonal plasma cells of patients with systemic light-chain (AL-) amyloidosis is associated with response to high-dose melphalan Journal Article

Authors: Zhou, P.; Teruya-Feldstein, J.; Lu, P.; Fleisher, M.; Olshen, A.; Comenzo, R. L.
Article Title: Calreticulin expression in the clonal plasma cells of patients with systemic light-chain (AL-) amyloidosis is associated with response to high-dose melphalan
Abstract: In high doses with stem-cell transplantation, melphalan is an effective but toxic therapy for patients with systemic light-chain (AL-) amyloidosis, a protein deposition and monoclonal plasma cell disease. Melphalan can eliminate the indolent clonal plasma cells that cause the disease, an achievement called a complete response. Such a response is usually associated with extended survival, while no response (a less than 50% reduction) is not. Gene-expression studies and a stringently supervised analysis identified calreticulin as having significantly higher expression in the pretreatment plasma cells of patients with systemic AL-amyloidosis who then had a complete response to high-dose melphalan. Calreticulin is a pleiotropic calcium-binding protein found in the endoplasmic reticulum and the nucleus whose overexpression is associated with increased sensitivity to apoptotic stimuli. Real-time PCR and immunohistochemical staining also showed that expression of calreticulin was higher in the plasma cells of those with a complete response. Furthermore, wild-type murine embryonic fibroblasts were significantly more sensitive to melphalan than calreticulin knock-out murine embryonic fibroblasts. These data have important implications for understanding the activity of melphalan in plasma-cell diseases and support further investigation of calreticulin and its modulation in patients with systemic AL-amyloidosis receiving high-dose melphalan. © 2008 by The American Society of Hematology.
Keywords: immunohistochemistry; clinical article; protein expression; treatment response; nonhuman; animal cell; animals; mice; mice, knockout; apoptosis; gene expression; cell line; melphalan; amyloidosis; stem cell transplantation; gene expression regulation; plasma cell; endoplasmic reticulum; reverse transcriptase polymerase chain reaction; staining; fibroblast; fibroblasts; embryo, mammalian; calcium binding protein; real time polymerase chain reaction; immunoglobulin light chains; transplantation, autologous; pleiotropy; plasma cells; calreticulin; myeloablative agonists; familial amyloidosis; nucleus accumbens
Journal Title: Blood
Volume: 111
Issue: 2
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2008-01-15
Start Page: 549
End Page: 557
Language: English
DOI: 10.1182/blood-2007-05-090852
PUBMED: 17982021
PROVIDER: scopus
PMCID: PMC2200859
Notes: --- - "Cited By (since 1996): 7" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Julie T Feldstein
    287 Feldstein
  2. Raymond L Comenzo
    111 Comenzo
  3. Ping Lu
    4 Lu
  4. Ping Zhou
    43 Zhou
  5. Adam B Olshen
    107 Olshen
  6. Martin Fleisher
    228 Fleisher