![]() Our work will uncover how manipulating the autophagic process can improve responses to PIs, and identify which patient subgroups may benefit from this approach. We are working to define the role of autophagy in mediating resistance to proteasome inhibitor therapy. This is exploited by the therapeutic use of proteasome inhibitors (PIs) that have transformed the outlook for many patients, however not all patients respond and many will develop resistance. One mechanism of resistance is the utilisation of an alternate protein degradation pathway, autophagy. Myeloma cells secrete excess monoclonal immunoglobulin and are uniquely dependent on protein processing pathways. Research project examples Enhancing the anti-myeloma activity of proteasome inhibition ![]() Recent work in newly diagnosed MM patients reveal the presence of dysfunctional marrow resident effector cells that influence clinical outcomes, and we are investigating the role of changes in bone marrow immune function when patients progress from smouldering to active symptomatic multiple myeloma. Work is also focused on the role of immune dysfunction and progression of myeloma. Refinement of CAR-T approaches, and exploration of novel targets remains at the forefront of our work. Current work is focused on optimising cellular therapies through improved understanding of the marrow immune environment, by interrogating patient bone marrow, and by using immune competent murine models. The Myeloma Immunotherapy group is led by Dr Lydia Lee. ![]() We work closely with the large clinical service at UCLH, and with national NCRN studies to interrogate the drivers of disease resistance and relapse, the benefit of early stem cell transplantation and the role of immunotherapeutic strategies in deepening disease response in the Myeloma XV trial in newly diagnosed patients. Our work utilises disease models such as cellular co-cultures, ex-vivo and in-vivo models, and these are interrogated using functional assays, high dimensional flow cytometry, CyTOF, immunohistochemistry, next generation sequencing and genetic modification. Myeloma is a genomically and biologically complex tumour, and we seek to discover new biomarkers for drug sensitivity and response to novel therapies. Our research has a strong translational focus to develop new anti-myeloma therapies, including cellular immunotherapies, and to advance early detection strategies for myeloma. Our work seeks to understand the role of the bone marrow microenvironment in promoting tumour growth and drug resistance, including mechanisms of immune dysfunction. Despite considerable therapeutic advances, myeloma remains incurable and most patients will die of their cancer. Myeloma is a cancer of plasma cells that expand in the bone marrow, causing bone marrow failure and bone destruction. All rights reserved.The Myeloma Laboratory at UCL aims to bring scientific endeavour to the clinic for patient benefit. ![]() Immunofixation International Myeloma Working Group Laboratory medicine Myeloma Protein electrophoresis sFLC. However, we anticipate new tests and technologies to become available in the future with improved analytical sensitivity, as well as improved clinical sensitivity in identifying patients who are at high risk of progression to multiple myeloma. Laboratory testing in myeloma-related investigation relies on several traditional chemistry assays. Finally, we discuss the importance of communication in protein electrophoresis results, where laboratorians are required to relate clinically relevant myeloma-relevant information to the ordering physician on the background of a complex pattern of serum or urine proteins. Furthermore, we discuss other traditional chemistry assays essential to myeloma investigation, and potential interferences that may arise due to the disease nature of myeloma, that is, the presence of a monoclonal immunoglobulin. This includes the use and value of protein electrophoresis, serum free light chain and cytogenetic testing. Here, we have reviewed current literature and core guidelines on the details of laboratory testing in myeloma-related investigations. A variety of chemistry and molecular assays are routinely used to monitor patient progress, response to treatment and relapse. Laboratory testing plays an essential role in the diagnosis and management of patients with multiple myeloma.
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