Learning from Patients: The Interplay between Clinical and Laboratory Research in AL Amyloidosis

Moshe E Gatt,Marjorie Pick

doi:10.3390/hemato3010002

Moshe E Gatt, Marjorie Pick

Open Access

https://doi.org/10.3390/hemato3010002

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Journal: Hemato	Publication Date: Dec 22, 2021
Citations: 1	License type: CC BY 4.0

Affiliation: Hadassah Medical Center, Hebrew University of Jerusalem

Abstract

Primary systemic light chain amyloidosis (AL) is a rare monoclonal plasma cell disorder. Much research has been performed to determine the factors that underly amyloidogenicity. However, there is increasing evidence that the primary clone, and also patient-related factors, influence the mechanism and rate of the process. The lessons learnt from patient care definitely imply that this is not solely due to the deposition of material in the tissues that cause organ injury but amyloid light chain precursors are likely to mediate cellular toxicity. The disease rarity, combined with the lack of in vitro tools, and that multi-organ failure has a wide clinical spectrum, result in investigative challenges and treatment limitations (due to AL patient frailty). All these characteristics make the disease difficult to diagnose and indicate the need to further study its origins and treatments. This review will focus on the various aspects of the amyloidogenic plasma cell clone, as learnt from the patient care and clinics, and its implications on basic as well as clinical trials of AL research. Details regarding the etiology of the plasma cell clone, understanding the diagnosis of AL, and improvement of patient care with specific consideration of the future perspectives of individualized patient therapy will be described.

Highlights

Much research has been performed to determine the factors that underly amyloidogenicity
To paraphrase the first sentence of Lev Tolstoy’s novel Anna Karenina: “Happy families are all alike; every unhappy family is unhappy in its own way”, we may say: “Normal plasma cells are all alike; every amyloidotic plasma cell is dysfunctional in its own way.”
There are multiple levels of challenges: how pathological is the clone in contrast to the pathologic protein? Is primary amyloidosis (AL) just a misfolded protein monoclonal gammopathy of unknown significance (MGUS) type of disease, or does the plasma cell clone have a unique etiology and therapeutic importance? Can we recognize the true pathological clone—at the plasma cell level or the protein level? Are patients with multiple myeloma (MM) the same as AL patients? Lessons learnt and accumulating from the clinics and laboratory show the amyloid producing plasma cell clones are unique

Summary

Introduction

To paraphrase the first sentence of Lev Tolstoy’s novel Anna Karenina: “Happy families are all alike; every unhappy family is unhappy in its own way”, we may say:. “Normal plasma cells are all alike; every amyloidotic plasma cell is dysfunctional in its own way.”. In this respect, it is remarkable to note that each patient has a different disease—. Different pace, organ involvement, extent, symptoms, and even response to the treatments. This makes amyloidosis an even rarer disease that is so difficult to study. Is primary amyloidosis (AL) just a misfolded protein monoclonal gammopathy of unknown significance (MGUS) type of disease, or does the plasma cell clone have a unique etiology and therapeutic importance? Lessons learnt and accumulating from the clinics and laboratory show the amyloid producing plasma cell clones are unique.

The Amyloidogenic Clone

The Clonal Distinction of AL PCs May Aid in Diagnosis

The Plasma Cell Clonal Features Aid in the Individual Patient Treatment

The Patient’s Burden of AL on Health-Related Quality of Life

Findings

From the Patient to the Bench Side