Bortezomib-adapted cell lines display a plasmacytic phenotype. (A-C) Gene expression signatures of plasma-cell differentiation distinguish bortezomib-adapted HBL2-BR (A, C) and JEKO-BR cell lines (B) from the respective PT cell lines. The leading edge of each gene set is displayed in a heat map. Changes in the expression of selected B-cell and plasma-cell surface markers were confirmed by flow cytometry. (D) Early differentiation genes³⁵  variably expressed between the PT and BR cell lines. Of the 50 genes described in the signature, 43 were expressed in the MCL cell lines. Shown are genes with at least a 1.2-fold change in expression: down-regulation for genes expressed in B cells and up-regulation for genes expressed in plasma cells. (E) BLIMP and IRF4 expression in nuclear fractions from PT and BR cell lines assessed by Western blot using TBP as a loading control. (F) HBL2-BR cells were maintained in culture with (HBL2-BR) or without 100nM bortezomib (HBL2-BR Bzm washout) for 2 months. The expression of B-cell and plasma-cell surface markers assessed by flow cytometry in these and the PT cell line (HBL2-PT) are shown.