Constitutively active FGFR3 with Lys650Glu mutation enhances bortezomib sensitivity in plasma cell malignancy.

Unlabelled: The ectopically expressed fibroblast growth factor receptor 3 (FGFR3) and its constitutively active mutations have been detected in patients with multiple myeloma (MM). This study investigated whether the cytotoxic effects of bortezomib on malignant plasma cells are associated with FGFR3 expression and the existence of mutations of FGFR3.

Materials And Methods: Cell apoptosis assays were performed in a plasmacytoma cell line, FR4 cells and a myeloma cell line, RPMI8226 cells overexpressing wild-type FGFR3 (FGFR3(WT)) or two different mutants, FGFR3(K650E) or FGFR3(Y373C), and the induction of endoplasmic reticulum (ER) stress protein was compared between each type of cell.

Myeloid neoplasm-related gene abnormalities differentially affect dendritic cell differentiation from murine hematopoietic stem/progenitor cells.

Dendritic cells (DCs) play important roles in tumor immunology. Leukemic cells in patients with myeloid neoplasms can differentiate into DCs in vivo (referred to as in vivo leukemic DCs), which are postulated to affect anti-leukemia immune responses. We established a reproducible culture system of in vitro FLT3 ligand-mediated DC (FL-DC) differentiation from murine lineage(-) Sca-1(+) c-Kit(high) cells (LSKs), which made it possible to analyse the effects of target genes on steady-state DC differentiation from hematopoietic stem/progenitor cells.