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, Diane F Jelinek

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 Na 2SO 4. 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.

Original languageEnglish (US)
Pages (from-to)1931-1941
Number of pages11
JournalBlood
Volume112
Issue number5
DOIs
StatePublished - Sep 1 2008

Fingerprint

Cells
Light
Cell Line
Amyloid
Amyloidosis
Immunoglobulin Light Chains
Plasma Cells
Immunoglobulin Light Chain Genes
Cytology
Amyloidogenic Proteins
Plasmas
Natural History
Cell Biology
Tumors
Genes
Display devices
Phenotype
Kinetics
Growth
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Biologic and genetic characterization of the novel amyloidogenic lambda light chain-secreting human cell lines, ALMC-1 and ALMC-2. / Arendt, Bonnie K.; Ramirez-Alvarado, Marina; Sikkink, Laura A.; Keats, Jonathan J.; Ahmann, Gregory J.; Dispenzieri, Angela; Fonseca, Rafael; Ketterling, Rhett P.; Knudson, Ryan A.; Mulvihill, Erin M.; Tschumper, Renee C.; Wu, Xiaosheng; Zeldenrust, Steven R.; Jelinek, Diane F.

In: Blood, Vol. 112, No. 5, 01.09.2008, p. 1931-1941.

Research output: Contribution to journalArticle

Arendt, BK, Ramirez-Alvarado, M, Sikkink, LA, Keats, JJ, Ahmann, GJ, Dispenzieri, A, Fonseca, R, Ketterling, RP, Knudson, RA, Mulvihill, EM, Tschumper, RC, Wu, X, Zeldenrust, SR & Jelinek, DF 2008, 'Biologic and genetic characterization of the novel amyloidogenic lambda light chain-secreting human cell lines, ALMC-1 and ALMC-2', Blood, vol. 112, no. 5, pp. 1931-1941. https://doi.org/10.1182/blood-2008-03-143040
Arendt, Bonnie K. ; Ramirez-Alvarado, Marina ; Sikkink, Laura A. ; Keats, Jonathan J. ; Ahmann, Gregory J. ; Dispenzieri, Angela ; Fonseca, Rafael ; Ketterling, Rhett P. ; Knudson, Ryan A. ; Mulvihill, Erin M. ; Tschumper, Renee C. ; Wu, Xiaosheng ; Zeldenrust, Steven R. ; Jelinek, Diane F. / Biologic and genetic characterization of the novel amyloidogenic lambda light chain-secreting human cell lines, ALMC-1 and ALMC-2. In: Blood. 2008 ; Vol. 112, No. 5. pp. 1931-1941.
@article{edcfada8bd1f4905ada9883d3f6258d3,
title = "Biologic and genetic characterization of the novel amyloidogenic lambda light chain-secreting human cell lines, ALMC-1 and ALMC-2",
abstract = "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 Na 2SO 4. 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.",
author = "Arendt, {Bonnie K.} and Marina Ramirez-Alvarado and Sikkink, {Laura A.} and Keats, {Jonathan J.} and Ahmann, {Gregory J.} and Angela Dispenzieri and Rafael Fonseca and Ketterling, {Rhett P.} and Knudson, {Ryan A.} and Mulvihill, {Erin M.} and Tschumper, {Renee C.} and Xiaosheng Wu and Zeldenrust, {Steven R.} and Jelinek, {Diane F}",
year = "2008",
month = "9",
day = "1",
doi = "10.1182/blood-2008-03-143040",
language = "English (US)",
volume = "112",
pages = "1931--1941",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

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 Na 2SO 4. 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 Na 2SO 4. 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

VL - 112

SP - 1931

EP - 1941

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -