SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Comenzo, R. L. Articles by Herrera, G. A. Search for Related Content PubMed PubMed Citation Articles by Comenzo, R. L. Articles by Herrera, G. A. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2001, Vol. 98, No. 3, pp. 714-720 IMMUNOBIOLOGY The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig VL germ line gene use and clonal plasma cell burden Raymond L. Comenzo, Yana Zhang, Carmen Martinez, Keren Osman, and Guillermo A. Herrera From the Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; the Hospital Clinic of Barcelona, Catalonia, Spain; and the Department of Pathology, Medicine and Cell Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport. Primary systemic amyloidosis (AL) is a protein conformation disorder in which monoclonal immunoglobulin light chains produced by clonal plasma cells are deposited as amyloid in the kidneys, heart, liver, or other organs. Why patients with AL present with amyloid disease that displays such organ tropism is unknown. This study tested the hypothesis that both the light-chain variable region (Ig VL) germ line genes used by AL clones and the plasma cell burden influenced AL organ tropism. To assess the renal tropism of some light chains, an in vitro renal mesangial cell model of amyloid formation was used. With reverse transcription-polymerase chain reaction, Ig VL genes were sequenced from 60 AL patients whose dominant involved organs were renal (52%), cardiac (25%), hepatic (8%), peripheral nervous system (8%), and soft tissue and other (7%). Patients with clones derived from the 6a VVI germ line gene were more likely to present with dominant renal involvement, whereas those with clones derived from the 1c, 2a2, and 3r V genes were more likely to present with dominant cardiac and multisystem disease. Patients with V clones were more likely to have dominant hepatic involvement and patients who met the Durie criteria for myeloma (38%, 23 of 60) were more likely to present with dominant cardiac involvement independent of germ line gene use. In the in vitro model, unlike all other AL light chains tested, VI light chains formed amyloid rapidly both with and without amyloid-enhancing factor. These data support the hypothesis that germ line gene use and plasma cell burden influence the organ tropism of AL. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Hadzidimitriou, N. Darzentas, F. Murray, T. Smilevska, E. Arvaniti, C. Tresoldi, A. Tsaftaris, N. Laoutaris, A. Anagnostopoulos, F. Davi, et al. Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia Blood, January 8, 2009; 113(2): 403 - 411. [Abstract] [Full Text] [PDF] B. K. Arendt, M. Ramirez-Alvarado, L. A. Sikkink, J. J. Keats, G. J. Ahmann, A. Dispenzieri, R. Fonseca, R. P. Ketterling, R. A. Knudson, E. M. Mulvihill, et al. Biologic and genetic characterization of the novel amyloidogenic lambda light chain-secreting human cell lines, ALMC-1 and ALMC-2 Blood, September 1, 2008; 112(5): 1931 - 1941. [Abstract] [Full Text] [PDF] T. Bochtler, U. Hegenbart, F. W. Cremer, C. Heiss, A. Benner, D. Hose, M. Moos, J. Bila, C. R. Bartram, A. D. Ho, et al. Evaluation of the cytogenetic aberration pattern in amyloid light chain amyloidosis as compared with monoclonal gammopathy of undetermined significance reveals common pathways of karyotypic instability Blood, May 1, 2008; 111(9): 4700 - 4705. [Abstract] [Full Text] [PDF] P. Zhou, R. L. Comenzo, A. B. Olshen, E. Bonvini, S. Koenig, P. G. Maslak, M. Fleisher, J. Hoffman, S. Jhanwar, J. W. Young, et al. CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy Blood, April 1, 2008; 111(7): 3403 - 3406. [Abstract] [Full Text] [PDF] T. Bupha-Intr, J. W. Holmes, and P. M. L. Janssen Induction of hypertrophy in vitro by mechanical loading in adult rabbit myocardium Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3759 - H3767. [Abstract] [Full Text] [PDF] L. M. Dember Amyloidosis-Associated Kidney Disease J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3458 - 3471. [Abstract] [Full Text] [PDF] V. Sanchorawala Light-Chain (AL) Amyloidosis: Diagnosis and Treatment Clin. J. Am. Soc. Nephrol., November 1, 2006; 1(6): 1331 - 1341. [Abstract] [Full Text] [PDF] S. V. Rajkumar, A. Dispenzieri, and R. A. Kyle Monoclonal Gammopathy of Undetermined Significance, Waldenstrom Macroglobulinemia, AL Amyloidosis, and Related Plasma Cell Disorders: Diagnosis and Treatment Mayo Clin. Proc., May 1, 2006; 81(5): 693 - 703. [Abstract] [Full Text] [PDF] R. L. Comenzo, P. Zhou, M. Fleisher, B. Clark, and J. Teruya-Feldstein Seeking confidence in the diagnosis of systemic AL (Ig light-chain) amyloidosis: patients can have both monoclonal gammopathies and hereditary amyloid proteins Blood, May 1, 2006; 107(9): 3489 - 3491. [Abstract] [Full Text] [PDF] R. S. Abraham, K. V. Ballman, A. Dispenzieri, D. E. Grill, M. K. Manske, T. L. Price-Troska, N. G. Paz, M. A. Gertz, and R. Fonseca Functional gene expression analysis of clonal plasma cells identifies a unique molecular profile for light chain amyloidosis Blood, January 15, 2005; 105(2): 794 - 803. [Abstract] [Full Text] [PDF] L. Novak, W. J. Cook, G. A. Herrera, and P. W. Sanders AL-amyloidosis is underdiagnosed in renal biopsies Nephrol. Dial. Transplant., December 1, 2004; 19(12): 3050 - 3053. [Abstract] [Full Text] [PDF] G. Merlini and V. Bellotti Molecular Mechanisms of Amyloidosis N. Engl. J. Med., August 7, 2003; 349(6): 583 - 596. [Full Text] [PDF] P. Zhou, Y. Zhang, C. Martinez, N. Kalakonda, S. D. Nimer, and R. L. Comenzo Melphalan-mobilized blood stem cell components contain minimal clonotypic myeloma cell contamination Blood, July 15, 2003; 102(2): 477 - 479. [Abstract] [Full Text] [PDF] R. S. Abraham, S. M. Geyer, T. L. Price-Troska, C. Allmer, R. A. Kyle, M. A. Gertz, and R. Fonseca Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL) Blood, May 15, 2003; 101(10): 3801 - 3807. [Abstract] [Full Text] [PDF] A. Lebeau, E. Zeindl-Eberhart, E.-C. Muller, J. Muller-Hocker, P. R. Jungblut, B. Emmerich, and U. Lohrs Generalized crystal-storing histiocytosis associated with monoclonal gammopathy: molecular analysis of a disorder with rapid clinical course and review of the literature Blood, August 13, 2002; 100(5): 1817 - 1827. [Abstract] [Full Text] [PDF] V. Perfetti, S. Casarini, G. Palladini, M. C. Vignarelli, C. Klersy, M. Diegoli, E. Ascari, and G. Merlini Analysis of Vlambda -Jlambda expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambda III) as a new amyloid-associated germline gene segment Blood, July 18, 2002; 100(3): 948 - 953. [Abstract] [Full Text] [PDF] R. L. Comenzo and M. A. Gertz Autologous stem cell transplantation for primary systemic amyloidosis Blood, May 29, 2002; 99(12): 4276 - 4282. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020