Immunoglobulin light chain (AL) amyloidosis is caused by a typically small, minimally proliferating bone marrow plasma cell clone secreting a patient-unique, unstable, aggregation-prone, toxic light chain (LC). The amyloidogenicity of LCs is encrypted in their sequence, yet molecular determinants of LC pathogenicity remain obscure. N-glycosylation has been long suspected to be a determinant of LC amyloidogenicity based on anecdotal reports of individual AL patients with a clonal LC displaying this post-translational modification. It is hypothesized that N-glycosylation fundamentally contributes to determining the amyloidogenicity of immunoglobulin LCs in a subset of patients with AL and might influence its clinical phenotype. It is further proposed that the synthesis and secretion of unstable LCs that also have to be N-glycosylated might reverberate on the biology of the plasma cell clone, possibly modulating the sensitivity toward different drugs and might represent itself a therapeutic target.

The objective of our study is now to elucidate the molecular role of LC N-glycosylation in AL amyloidosis, exploit it for risk assessment, and define its potential impact on the biology of the underlying plasma cell clone and its drug sensitivity.

Inclusion Criteria:

• Diagnosis of monoclonal gammopathy (e.g. AL amyloidosis, MGUS, MM, others)
• Planned peripheral blood sampling +/- bone marrow aspiration
• Age > 18 years
• Willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes through signing a written informed consent.

Exclusion Criteria:

• Lack of monoclonal gammopathy
• Patients fulfilling the criteria for complete hematologic response after anti-clonal therapy
• Age <18 years
• Failure to show willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes.

Treatment-naïve patients with AL amyloidosis or other monoclonal gammopathies