Multiple myeloma (MM) holds a unique position amongst haematological malignancies owing to the presence of accessible biomarkers of disease, namely clonal intact immunoglobulin and/or clonotypic kappa or lambda light chains in the serum. Quantitation of these biomarkers enables both disease monitoring and response attribution. However, with increasingly efficacious therapeutics deeper levels of response, not able to be defined by conventional serum biomarker quantitation, namely measurable residual disease (MRD) positivity or negativity, with the latter being a powerful indicator of extended disease-free survival, are being used. Both next generation sequencing (NGS) and multi-parameter flow cytometry (next generation flow - NGF) evaluation of bone marrow aspirates are utilised for MRD determination. The pitfalls of both approaches include the invasive nature of the test, high dependence on sample quality and the inability to overcome the spatial heterogeneity of MM within the intramedullary compartment. In this context, a range of highly sensitive blood-based mass spectrometric approaches have been evaluated with varying costs, complexity and sensitivity, and have clearly demonstrated a high level of utility that will hopefully obviate the need for bone marrow biopsies in the determination of MM disease response within the coming decade. 

Amyloidosis subtyping by laser-capture microdissection and tandem mass spectrometry

Peter Mollee¹

¹ Pathology Queensland and Queensland Amyloidosis Centre, Princess Alexandra Hospital, Brisbane, Australia

 

Amyloidosis is a rare but devastating condition caused by deposition of misfolded proteins as aggregates in the extracellular tissues of the body, leading to impairment of organ function. Many, but not a limitless number of proteins can cause amyloidosis, the most common being transthyretin (ATTR), immunoglobulin light chain (AL), serum amyloid A protein (AA) and the alpha chain of fibrinogen (AFib). For patients with systemic amyloidosis, unequivocal identification of the amyloid type is mandatory for optimal treatment.

 

Mass spectrometry-based proteomics has become the new gold standard for amyloid typing, used in conjunction with current clinical and antibody-based tests. This proteomic diagnostic method has been developed at the Queensland Amyloidosis Centre in Brisbane as a collaboration between Pathology Queensland and the Translational research Institute. It involves an initial selection of amyloid deposits from formal-fixed paraffin-embedded tissue biopsy samples by laser-capture microdissection followed by high performance liquid chromatography and tandem mass spectrometry, and then bioinformatic analysis to details the protein composition of the dissected amyloid. In light of its clear benefit to patients, and with the availability of new treatments for specific amyloid types, mass spectrometry based proteomics for amyloid typing should be implemented broadly.