SEARCH:   Advanced

Blood, 1 September 2008, Vol. 112, No. 5, pp. 1931-1941. Prepublished online as a Blood First Edition Paper on June 20, 2008; DOI 10.1182/blood-2008-03-143040. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2008-03-143040v1 112/5/1931    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Arendt, B. K Articles by Jelinek, D. F Search for Related Content PubMed PubMed Citation Articles by Arendt, B. K Articles by Jelinek, D. F Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 3, 2008 Accepted May 26, 2008 Biologic and genetic characterization of the novel amyloidogenic lambda light chain-secreting human cell lines, ALMC-1 and ALMC-2 Bonnie K Arendt, Marina Ramirez-Alvarado, Laura A Sikkink, Jonathan J Keats, Gregory J Ahmann, Angela Dispenzieri, Rafael Fonseca, Rhett P Ketterling, Ryan A Knudson, Erin M Mulvihill, Renee C Tschumper, Xiaosheng Wu, Steven R Zeldenrust, and Diane F Jelinek* Department of Immunology, Mayo Clinic, Rochester, MN, United States Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United States Comprehensive Cancer Center, Mayo Clinic, Scottsdale, AZ, United States Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States * Corresponding author; email: jelinek.diane{at}mayo.edu. Primary systemic amyloidosis (AL) is a rare monoclonal plasma cell (PC) disorder characterized by the deposition of misfolded immunoglobulin (Ig) light chains (LC) in vital organs throughout the body. To our knowledge, no cell lines have ever been established from AL patients. Here we describe the establishment of the ALMC-1 and ALMC-2 cell lines from an AL patient. Both cell lines exhibit a PC phenotype and display cytokine-dependent growth. Using a comprehensive genetic approach, we established the genetic relationship between the cell lines and the primary patient cells and we were also able to identify new genetic changes accompanying tumor progression that may explain the natural history of this patient's disease. Importantly, we demonstrate that free lambda LC secreted by both cell lines contained a beta structure and formed amyloid fibrils. Despite absolute Ig LC variable gene sequence identity, the proteins show differences in amyloid formation kinetics that are abolished by the presence of Na2SO4. The formation of amyloid fibrils from these naturally secreting human LC cell lines is unprecedented. Moreover, these cell lines will provide an invaluable tool to better understand AL, from the combined perspectives of amyloidogenic protein structure and amyloid formation, genetics, and cell biology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020