Systemic immunoglobulin light chain amyloidosis

  title={Systemic immunoglobulin light chain amyloidosis},
  author={Giampaolo Merlini and Angela Dispenzieri and Vaishali Sanchorawala and Stefan O. Sch{\"o}nland and Giovanni Palladini and Philip N. Hawkins and Morie A. Gertz},
  journal={Nature Reviews Disease Primers},
Systemic immunoglobulin light chain amyloidosis is a protein misfolding disease caused by the conversion of immunoglobulin light chains from their soluble functional states into highly organized amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of which cardiac damage and renal damage predominate. The development of novel sensitive biomarkers and imaging technologies for the… 
Monitoring Patients with Light Chain (AL) Amyloidosis during and after Therapy: Response Assessment and Identification of Relapse
The validated response criteria is described and the future direction for the definition of progression criteria in this disease is reported on.
Novel challenges in the management of immunoglobulin light chain amyloidosis: from the bench to the bedside
An update on the recent hot topics as novel therapeutic approaches, definition of relapse, and hematologic response assessment are presented, as well as new sensitive techniques, as mass spectrometry approach and bone marrow minimal residual disease assessment, are available to evaluate depth of response.
Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications
A framework of AL classification based on genetic aberrations is proposed and the amyloid formation of AL from a genetic aspect is discussed.
Stabilization of amyloidogenic immunoglobulin light chains by small molecules
Small-molecule kinetic stabilizers of the native dimeric structure of full-length LCs are introduced, which can slow or stop the amyloidogenicity cascade at its origin, a proven strategy to ameliorate postmitotic tissue degeneration.
Supportive Care for Patients with Systemic Light Chain Amyloidosis.
Dissecting the Molecular Features of Systemic Light Chain (AL) Amyloidosis: Contributions from Proteomics
This review will provide an overview of the major achievements of proteomic studies in AL amyloidosis, with a presentation of the most recent acquisitions and a critical discussion of open issues and ongoing trends.


Systemic light chain amyloidosis: an update for treating physicians.
In immunoglobulin light chain amyloidosis a small, indolent plasma cell clone synthesizes light chains that cause devastating organ damage and novel agents and therapeutic targets are expected to be exploited, in an integrated, more effective and less toxic treatment strategy.
What is new in diagnosis and management of light chain amyloidosis?
Screening of early organ damage based on biomarkers can help identify patients with monoclonal gammopathy of undetermined significance who are developing AL amyloidosis before they become symptomatic.
AL amyloidosis: from molecular mechanisms to targeted therapies.
  • G. Merlini
  • Medicine, Biology
    Hematology. American Society of Hematology. Education Program
  • 2017
The future of AL amyloidosis treatment is combination therapy and will require an innovative collaborative model for a rapid translation from bench to bedside with the ultimate aim of achieving a cure for this complex disease.
Systemic amyloidosis
Effect of Dose-Intensive Intravenous Melphalan and Autologous Blood Stem-Cell Transplantation on AL AmyloidosisAssociated Renal Disease
D dose-intensive intravenous melphalan with autologous blood stem-cell support is used to eliminate the clonally expanded plasma cells that produce the amyloidogenic light chains, thereby preventing further amyloids deposition into vital organs.
Immunotherapy in systemic primary (AL) amyloidosis using amyloid-reactive monoclonal antibodies.
Demonstration of the therapeutic efficacy of this amyloid-reactive mAb would provide an important proof-of-principle that this form of immunotherapy also could benefit individuals with other types of inherited or acquired amyloids-associated disease.
Increased serum free light chains precede the presentation of immunoglobulin light chain amyloidosis.
  • B. Weiss, Joseph Hebreo, S. Olson
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2014
Increase of FLCs, including within the accepted normal range, precedes the development of AL amyloidosis for many years.
Novel mitochondrial protein interactors of immunoglobulin light chains causing heart amyloidosis
It is shown that cardiotoxic LCs establish nonphysiologic protein‐protein contacts in human cardiac cells, offering new clues on the pathogenesis of AL cardiomyopathy.
Amyloidosis in autoinflammatory syndromes.
Concurrent structural and biophysical traits link with immunoglobulin light chains amyloid propensity
The comprehensive approach shows that low fold stability and high protein dynamics correlate with amyloidogenic LCs, while hydrophobicity, structural rearrangements and nature of the LC dimeric association interface do not appear to play a significant role in defining amyloids propensity.