Figure 3.

Differential myeloma drug sensitivity profiles of malignant subpopulations at diagnosis. A, Flow cytometry showed a monotypic population by typical markers CD138 and CD38 (left), but showed rarer subpopulations with CD45 expression, with or without CD19 (right) that were not detected by scRNA-seq. B, Of the cell surface proteins measured by flow cytometry, the mRNA for CD46 showed the most differential expression (l₂FC = 0.44, P = 5.76 × 10⁻⁷) between the LCE-multiple myeloma (MM) and IGH-MM subpopulations. C, Relatively CD46-high and CD46-low populations were divided to approximate subpopulation drug sensitivity of IGH-MM and LCE-MM, respectively. D, The drug sensitivity profiles implied that the CD46-high/IGH-MM subpopulation had a primary IMiD refractory phenotype and was relatively less bortezomib sensitive compared with LCE-MM (n = 3, tested by t test, bars depict standard deviation. *, P < 0.05; ***, P < 0.001). Bor, bortezomib; Car, carfilzomib; Dara, daratumumab; Len, lenalidomide; norm %, percent viability normalized to untreated controls; Pom, pomalidomide.