Waldenström macroglobulinaemia and IgM monoclonal gammopathy of undetermined significance: emerging understanding of a potential precursor condition

Abstract

Previously thought to be best described as a plasma cell disorder, Waldenström macroglobulinaemia (WM) is now understood to be a distinct clinicobiological entity. WM shares B-cell origin and certain other features with both chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). WM and CLL arise from B-cells at discrete stages in their maturation process, and MM arises from B-cells that have fully differentiated into plasma cells. While MM has a well-known precursor condition, monoclonal gammopathy of undetermined significance (MGUS), CLL and WM may also have associated precursor states, monoclonal B-cell lymphocytosis (MBL) and IgM MGUS, respectively. This review explores the features that link or distinguish these haematolymphoid malignancies, with special attention to emerging data regarding IgM MGUS and its unique relationship to WM, and identifies important gaps in our understanding of the putative precursor conditions, MBL and IgM MGUS.