19.2. Clonal populations in multiple myeloma

Chapter 19

MM patients can be classified according to their monoclonal protein type, i.e. intact immunoglobulin MM (IIMM; Chapter 17), light chain MM (LCMM; Chapter 15) and nonsecretory MM (NSMM; Chapter 16) [425]. At presentation, 95% of IIMM patients also have an abnormal κ/λ serum free light chain (sFLC) ratio (Section 17.2). The simplest interpretation is that most IIMM patients have a single MM clone producing monoclonal intact immunoglobulin plus free light chains (FLCs). However, specific methods of plasma cell staining have challenged this idea. Ayliffe et al. [367][368] performed double immunofluorescence staining to study immunoglobulin heavy chain and light chain expression by plasma cells in bone marrow biopsies. The majority of patients had a single tumour cell population that expressed either monoclonal intact immunoglobulins and FLCs (42%), intact immunoglobulins alone (32%), or FLCs alone (8%). However, in the remaining 18% of patients, separate clones expressing either intact immunoglobulin or FLC only were identified (Figure 19.2). These dual clonal populations were the first indicators that, within a single patient, multiple clones expressing different monoclonal proteins could be found. Subsequently, using array comparative genomic hybridisation (aCGH) and fluorescence in situ hybridisation (FISH), Keats et al. [426] elegantly demonstrated the presence of multiple clones in a patient with IgA MM. The impact of these multiple clones is illustrated in the clinical case history below.