High Notch1, Notch2, and Jagged1 expression in primary MM cells. (A-H) Bone marrow biopsy specimen of one case of MM. (A) Giemsa staining demonstrating bone marrow infiltration by atypical plasma cells (MM cells) with large nuclei and prominent nucleoli. (B) Immunostained MM cells show monotypic expression of immunoglobulin light-chain κ. (C-D) Immunostains for myeloperoxidase (C) and glycophorin C (D) mark granulocytic and erythroid precursors showing that MM cells are surrounded by nonmalignant bone marrow cells. (E-F) Double labeling for CD138 (brown reaction product; streptavidin/biotin/peroxidase technique) and Notch1 (red reaction product; immunoalkaline phosphatase method) reveals that CD138⁺ MM cells strongly coexpress Notch1. (G-H) Double labeling for CD138 (brown reaction product) and the Notch ligand Jagged1 (red reaction product) demonstrates coexpression of CD138 and Jagged1 on MM cells. (F,H) Some CD138^- nonmalignant bone marrow cells, mainly megakaryocytes, show weak immunoreactivity against Notch1 or Jagged1. (I-K) Extramedullar (liver) biopsy specimen of MM immunostained for Notch1 (I), Notch2 (J), and Jagged1 (K) and counterstained with hematoxylin. MM cells are intensely labeled by anti-Notch1, anti-Notch2, and anti-Jagged1 antibodies. (L-N). Isolated plasma cells (CD38⁺⁺⁺/CD19⁺) from the nonneoplastic bone marrow of healthy donors (cytospins) show low to undetectable immunoreactivity against Notch1 (L), Notch2 (M), and Jagged1 (N). Original magnification × 200.