Hypothesis for the 2 pathogenesis pathways for MM. According to our results, the natural hypothesis is to postulate 2 fundamentally separate pathways for the pathogenesis of MM. This hypothesis is based on the close relationship of ploidy category to the presence of the recurrent IgH translocations. While most patients in the nonhyperdiploid group have IgH translocations, patients in the hyperdiploid group have more trisomies, and both conditions might arise from similar clones observed at the MGUS stage. Each of the 2 pathways could be independent, but it is possible that in some cases the nonhyperdiploid could lose an IgH translocation and give rise to the hyperdiploid variant MM (dashed arrow). It is currently unknown if this ploidy and IgH association is also seen in MGUS.