By detailed sequence analysis and subsequent biophysical characterization of prototypic light chains, this project aims to identify sequence fingerprints in IGLV1-44 light chains leading to AL amyloidosis and POEMS syndrome. This understanding might help improve the risk stratification and early diagnosis of patients overexpressing pathologic IGLV1-44 LCs. Moreover, the development of nanobodies efficient in recognizing and stabilizing IGLV1-44 light chains which exert direct toxicity in cardiac AL amyloidosis and POEMS syndrome might form the basis for future development of therapeutic agents capable of counteracting IGLV1-44 light chain proteotoxicity.

Inclusion Criteria:

• Biopsy-proven diagnosis of systemic AL amyloidosis, POEMS syndrome or multiple myeloma
• 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:

• Undefined monoclonal gammopathy or non-AL amyloidosis
• 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.

Patients with biopsy-proven diagnosis of systemic AL amyloidosis, POEMS syndrome or multiple myeloma