Figure 6.

The LCE-multiple myeloma (MM) subpopulation conferred a poor prognosis and represented a genetic subclone of MM cells. A, FGFR3 expression distribution was high across all MM cells at diagnosis, but low or undetectable in normal cell populations, supporting clonal distribution of t(4;14) in all malignant cells. B and C, InferCNV analysis identified clonal chromosome 1 gain and chromosome 13 loss in both subpopulations, consistent with findings by FISH. D, Alluvial plot showing that seven subclones were present at diagnosis, five were eliminated with treatment, and two persisted across timepoints. E, InferCNV also identified a chromosome 19 gain that was subclonal and mostly specific to LCE-MM (left), and this increased in proportion with the disease progression (box and whiskers show median, quartiles, and 1.5 times the interquartile range). F, InferCNV also detected a chromosome 22 gain in a subset of LCE-MM at diagnosis (left), which increased in proportion over time. G, Hematoxylin and eosin staining of bone marrow samples contained some large plasmablasts at diagnosis, but at first relapse the bone marrow consisted of predominantly plasmablasts. H, Ki67 staining from samples at diagnosis were positive in 10% of cells, increased to 50%–60% at first relapse. Rel, relapse; R/R, relapsed/refractory timepoint.