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
. 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. 
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. 
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.