IgM AL amyloidosis: delineating disease biology and outcomes with clinical, genomic and bone marrow morphological features

Sidana, Surbhi; Larson, Daniel P.; Greipp, Patricia T.; He, Rong; McPhail, Ellen D.; Dispenzieri, Angela; Murray, David; Dasari, Surendra; Ansell, Stephen M.; Muchtar, Eli; Gonsalves, Wilson I.; Kourelis, Taxiarchis; Ramı́rez-Alvarado, Marina; Kapoor, Prashant; Rajkumar, S. Vincent; Lacy, Martha Q.; Buadi, Francis K.; Leung, Nelson; Kyle, Robert A.; Kumar, Shaji; King, Rebecca; Gertz, Morie A.

doi:10.1038/s41375-019-0667-6

Cited by 44 publications

(48 citation statements)

References 38 publications

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“…Monoclonal IgM-related light chain AL accounts for 6% of all cases of AL. 34 Several studies have shown that the pattern of organ involvement is different from non-IgM Amyloidosis, with higher frequencies of lung, soft tissue, and peripheral nervous system involvement, and lower frequencies of heart. 34,35 In these cases, PNP is usually due to amyloid deposition in the nerves.…”

Section: Amyloidosismentioning

confidence: 99%

Waldenström’s Macroglobulinemia: An Exploration into the Pathology and Diagnosis of a Complex B-Cell Malignancy

Askari

Rodríguez

2021

JBM

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After 77 years since the initial description, Waldenström macroglobulinemia (WM) remains as a bone marrow neoplastic disorder with lymphoplasmacytic differentiation oversecreting a monoclonal immunoglobulin M (IgM). However, many biological and genetic aspects of this entity have been unraveled and it is now easy to correctly diagnose patients with this illness. The diagnosis requires the presence of a monoclonal IgM component and bone marrow lymphoid infiltration must be demonstrated. In addition, other small B-cell lymphoid neoplasms with plasma cell differentiation must be discarded. Although the clinical picture is highly heterogeneous, the diagnosis is much easier today compared to the past, since now we can demonstrate the presence of somatic mutations, especially the L265P mutation in the MYD88 gene, highly characteristic of WM (>90% of the patients), followed by the WHIM-like mutations in the CXCR4 gene (~35%). The identification of these mutations is very important, because they can modulate the response to new treatments with Bruton's tyrosine kinase (BTK) inhibitors. Thus, the conventional prognostic factors that predict the outcome of these patients (anemia, thrombopenia, high M component, high B2M, and advanced age), must be complemented with the genetic evaluation of the patient, that can help us in the prediction of the risk of transformation from asymptomatic to symptomatic forms (Del6q) and/or from indolent forms of the disease to aggressive lymphomas (CD79b mutations).

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Section: Amyloidosismentioning

confidence: 99%

Waldenström’s Macroglobulinemia: An Exploration into the Pathology and Diagnosis of a Complex B-Cell Malignancy

Askari

Rodríguez

2021

JBM

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“…In 5–10% of cases, AL is caused by an IgM paraprotein, often secreted by a B-cell clone [60, 61] and rarely by a plasma cell clone. IgM AL is regarded as a distinct clinical entity with several clinical features and organ involvement patterns, which distinguish it from non-IgM AL amyloidosis.…”

Section: Prognostic Value Of Plasma Cellular Factors In Al Amyloidosismentioning

confidence: 99%

“…A revised staging system combining liver involvement and the presence of neuropathy with the established factors elevated NT-proBNP and troponin was proposed for this disease [61], but requires further validation. It is critical for the prognosis of IgM-AL that diagnosis and treatment is directed at the underlying clonal disease [60, 61].…”

Section: Prognostic Value Of Plasma Cellular Factors In Al Amyloidosismentioning

confidence: 99%

Prognosis and Staging of AL Amyloidosis

et al. 2020

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The treatment options for systemic light chain amyloidosis (AL) are currently widening in an unprecedented way, brought about by an expanding arsenal of anti-myeloma therapy as well as by novel approaches to target toxic light chains and, most recently, deposited amyloid directly. In this context, accurate estimates of prognosis in AL, which allow for reliable patient advice and for example comparison of different therapies, are particularly important to clinicians. Some biomarkers and especially the genetic background of the underlying clonal disease as evaluated by interphase fluorescence in situ hybridization even have predictive value, enabling an appropriate treatment selection. Derived from the most frequently involved organs in AL, heart and kidney, this review focuses on overall survival and renal survival. A comprehensive overview and summary of reported prognostic factors and biomarkers in AL is given and the most important and validated factors are highlighted. Finally, established staging systems in AL as well as validated and perspective response criteria are presented.

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“…Mantle cell lymphoma (MCL) has also been reported to be associated with IgM paraproteins although the clinical implications of this are not known [ 36 ]. ALA associated with IgM paraproteins appears to be a distinct entity with a greater incidence of soft tissue and nerve involvement than other subtypes of ALA [ 45 , 46 ]. Although rare, IgM paraproteins are also described in Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome [ 47 ].…”

Section: Summary Of Who and Imwg (International Myeloma Working Grmentioning

confidence: 99%

“…MALT: mucosa-associated lymphoid tissue. References: [ 23 , 24 , 32 , 38 , 40 , 45 , 48 , 49 , 50 ].…”

Section: Figurementioning

confidence: 99%

Immunoglobulin M Paraproteinaemias

Girard

Soekojo

Ooi

et al. 2020

Cancers

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Monoclonal paraproteinaemia is an increasingly common reason for referral to haematology services. Paraproteinaemias may be associated with life-threatening haematologic malignancies but can also be an incidental finding requiring only observation. Immunoglobulin M (IgM) paraproteinaemias comprise 15–20% of monoclonal proteins but pose unique clinical challenges. IgM paraproteins are more commonly associated with lymphoplasmacytic lymphoma than multiple myeloma and can occur in a variety of other mature B-cell neoplasms. The large molecular weight of the IgM multimer leads to a spectrum of clinical manifestations more commonly seen with IgM paraproteins than others. The differential diagnosis of B-cell and plasma cell dyscrasias associated with IgM gammopathies can be challenging. Although the discovery of MYD88 L265P and other mutations has shed light on the molecular biology of IgM paraproteinaemias, clinical and histopathologic findings still play a vital role in the diagnostic process. IgM secreting clones are also associated with a number of “monoclonal gammopathy of clinical significance” entities. These disorders pose a novel challenge from both a diagnostic and therapeutic perspective. In this review we provide a clinical overview of IgM paraproteinaemias while discussing the key advances which may affect how we manage these patients in the future.

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IgM AL amyloidosis: delineating disease biology and outcomes with clinical, genomic and bone marrow morphological features

Cited by 44 publications

References 38 publications

Waldenström’s Macroglobulinemia: An Exploration into the Pathology and Diagnosis of a Complex B-Cell Malignancy

Waldenström’s Macroglobulinemia: An Exploration into the Pathology and Diagnosis of a Complex B-Cell Malignancy

Prognosis and Staging of AL Amyloidosis

Immunoglobulin M Paraproteinaemias

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