Implications of heterogeneity on MRD detection. MM involvement may be patchy and involve extramedullary sites. All these lesions may be detected by whole body imaging modality such as PET-CT scan. Within the individual lesions, 2 dimensions of heterogeneity may exist in the population of tumor cells. On one hand, there may be clonal heterogeneity where related clones with different genetic composition may coexist. On the other hand, clonally related progenitor populations at earlier stage of differentiation may exist. Flow cytometry can detect the plasma cell component but not the precursor population while ASO-PCR can detect all the clonal cells including the precursor population but its applicability is limited. The development of NGS methods may allow utility in larger population of patients.
