TY - JOUR
T1 - Biologic and genetic characterization of the novel amyloidogenic lambda light chain-secreting human cell lines, ALMC-1 and ALMC-2
AU - Arendt, Bonnie K.
AU - Ramirez-Alvarado, Marina
AU - Sikkink, Laura A.
AU - Keats, Jonathan J.
AU - Ahmann, Gregory J.
AU - Dispenzieri, Angela
AU - Fonseca, Rafael
AU - Ketterling, Rhett P.
AU - Knudson, Ryan A.
AU - Mulvihill, Erin M.
AU - Tschumper, Renee C.
AU - Wu, Xiaosheng
AU - Zeldenrust, Steven R.
AU - Jelinek, Diane F.
PY - 2008/9/1
Y1 - 2008/9/1
N2 - 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 cytokinedependent 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.
AB - 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 cytokinedependent 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.
UR - http://www.scopus.com/inward/record.url?scp=52649129150&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52649129150&partnerID=8YFLogxK
U2 - 10.1182/blood-2008-03-143040
DO - 10.1182/blood-2008-03-143040
M3 - Article
C2 - 18567838
AN - SCOPUS:52649129150
SN - 0006-4971
VL - 112
SP - 1931
EP - 1941
JO - Blood
JF - Blood
IS - 5
ER -