Mutations: Transforming the Landscape of IgM Monoclonal Gammopathies.

The gene has a physiological role in the innate immune system. Somatic mutations in , including the most common L265P, have been associated with the development of certain types of lymphoma. is present in more than 90% of patients with Waldenström's macroglobulinemia (WM) and IgM monoclonal gammopathy of undetermined significance (IgM-MGUS). The absence of mutations in WM patients has been associated with a higher risk of transformation into aggressive lymphoma, resistance to certain therapies (BTK inhibitors), and shorter overall survival. The MyD88 signaling pathway has also been used as a target for specific therapies. In this review, we summarize the clinical applications of testing in the diagnosis, prognosis, follow-up, and treatment of patients. Although is not specific to WM, few tumors present a single causative mutation in a recurrent position. The role of the oncogene in the pathogenesis of WM is still unclear, especially considering that the mutation can be found in normal B cells of patients, as recently reported. This may have important implications for early lymphoma detection in healthy elderly individuals and for the treatment response assessment based on a analysis.