Primary (AL) Amyloidosis in Plasma Cell Disorders

Abstract

Primary (AL) amyloidosis is the most common form of systemic amyloidosis. The morbidity arises from extracellular deposition of immunoglobulin light chain (LC) fibrils in major organs, such as the kidneys, heart, and bowel. Organ dysfunction contributes to a high mortality and poor prognosis, with a median survival time of 1-2 years from diagnosis. Here, we present a 46-yearold man with an exceptional clinical course of an LC multiple myeloma with generalized amyloidosis, causing renal insufficiency, congestive heart failure, and complete intestinal necrosis. We have summarized recent knowledge on AL amyloidosis, its association with monoclonal gammopathies, clinical presentations, diagnostic tools, and treatment strategies. Our comprehensive overview of this rare and often fatal disease aims to increase the awareness of AL amyloidosis. This may facilitate earlier diagnosis, and thus allow initiation of prompt and specific therapies, which are indispensable in order to improve disease prognosis. The Oncologist 2006;11:824-830

Amyloid in bone marrow smears of patients affected by multiple myeloma

“…Although bone marrow involvement by amyloid seems frequent in multiple myeloma, it is reported that less than 10% of the patients affected by MM may have or develop systemic AL amyloidosis [1]: this would suggest a lack of prognostic significance, but the influence of chemotherapy cannot be precisely weighed.…”

“…The preliminary data available suggest that amyloid deposition in the marrow of myeloma patients is frequent, as it can be traced in nearly 40% of cases. We failed to find correlations between bone marrow amyloid deposits and immunoglobulin type, disease stage, plasma cells percentage, hemoglobin, calcium, creatinine, albumin, orIntroduction AL amyloidosis is the most frequent type of systemic amyloidosis in Western countries [1]. It is caused by tissueinfiltrating proteins derived from monoclonal immunoglobulin light chains, frequently observed in patients affected by multiple myeloma (MM) or, less frequently, by Waldenström's macroglobulinemia or other lymphoproliferative disorders [2].…”

“…AL amyloid is determined by proteins arranged in cross-β-pleated sheet structures. These fibrils are usually formed by N-terminal fragments of variable region of an immunoglobulin light chain, although they may occasionally include part of a constant region or are formed by whole light chain [1,4]. Only a small portion of light chain is able to form amyloid fibrils: this property is likely correlated with distinctive structural features of amyloidogenic light chains, as almost 70% of them are lambda isotype and the genes Vλ6a and Vλ3r encode 42% of these chains [5,6].…”

Site-directed Mutagenesis Reveals Regions Implicated in the Stability and Fiber Formation of Human λ3r Light Chains

“…ing V H , allowing its free secretion (9,10). The loss of the Ig heterotetrameric structure may contribute to the amyloidogenicity of light chain variable domains because the fibrils of most AL patients predominantly comprise a single variable domain (11).…”

Paraneoplastik özellik gösteren metabolik hastalıklar

“…Amiloidozlar, anormal yapıda fibriler proteinlerin, çeşitli doku ve organlarda depolanarak o organın fonksiyonlarını bozmasıyla ortaya çıkan bir grup hastalıktır [36][37][38] . Amiloid fibrilleri farklı protein prekürsörlerinden köken alır ve proteolizise dirençlidir 39 .…”