Supplemental Figure Legends Supplementary Figure 1. Immunophenotypic analysis and fractionation of myeloma/plasma cells (MM/PCs) and B cells in multiple myeloma patients. A. Morphology of CD138+/CD38high-fractionated MM/PCs and CD138-CD38low/-CD19+-fractionated B cells. Wright-Giemsa staining (40x magnification) B. Abnormal CD56 expression in CD138+/CD38high-fractionated myeloma cells. Bone marrow cells of CD56+ myeloma patients were co-stained with CD38, CD138 and CD56. Three representative data are seen out of six tested samples. Supplementary Figure 2. Serial engraftment of CD138+/CD38high tumor cells in mice with previously transplanted fetal human bone. CD138+ and CD138- cells of patient M24 were transplanted into RAG2/c- mice. A mouse transplanted with CD138+ cells had human CD138+ cells, while mice transplanted with CD138- cells had human CD19+CD38+CD138- cells. Only the CD138+ xenograft was serially transplantable. Supplementary Figure 3. Immunophenotypic heterogeneity of patient myeloma cells. Flow-cytometry scatter plots for four representative patient samples (M24, M04, M43, M48) that included heterogeneous CD138+ bone marrow cells, as indicated by the variable expression of CD19 and CD45. 1 Supplementary Figure 4. Engraftment of CD38highCD45low/- myeloma cells from patient M19 into RAG2-/c- mice bearing previously transplanted fetal human bone grafts. Bone marrow cells from patient M19 were fractionated into CD19+CD138- B cells, CD138+CD45+ plasmablasts (PB) and CD138+CD45- plasma cells (PC) prior to transplantation. Only CD138+ cells engrafted into the mice but only xenografts of CD45- plasma cells were clonally related to patient myeloma cells (M19 in Figure 2E). 2