"Krej\u010D\u00ED, Pavel" . . "Jove, R." . "IL-6 and downstream JAK-dependent signaling pathways have critical roles in the pathophysiology of multiple myeloma (MM). We investigated the effects of a novel small-molecule JAK inhibitor (AZD1480) on IL-6/JAK signal transduction and its biological consequences on the human myeloma-derived cell lines U266 and Kms. 11. At low micromolar concentrations, AZD1480 blocks cell proliferation and induces apoptosis of myeloma cell lines. These biological responses to AZD1480 are associated with concomitant inhibition of phosphorylation of JAK2, STAT3 and MAPK signaling proteins. In addition, there is inhibition of expression of STAT3 target genes, particularly Cyclin D2. Examination of a wider variety of myeloma cells (RPMI 8226, OPM-2, NCI-H929, Kms. 18, MM1. S and IM-9), as well as primary myeloma cells, showed that AZD1480 has broad efficacy. In contrast, viability of normal peripheral blood (PB) mononuclear cells and CD138(+) cells derived from healthy controls was not significantly inhibited."@en . . "14310" . "[E8E44D96493C]" . . "Leukemia" . "myeloma; JAK2; STAT3; FGFR3"@en . "Wu, J." . "216593" . . "Kowolik, C." . "1"^^ . "Yen, Y." . . "The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting insuppression of human myeloma cell growth and survival." . "25" . . . . "3" . . "Wang, Y." . "The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting insuppression of human myeloma cell growth and survival."@en . "The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting insuppression of human myeloma cell growth and survival." . . "Yu, H." . . "16"^^ . "Xin, H." . "Kretzner, L." . "Chen, L." . "RIV/00216224:14310/11:00050507" . "The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting insuppression of human myeloma cell growth and survival."@en . . . . "Forman, S." . . . "000288159500017" . "Kujawski, M." . "Scuto, A." . "Popplewell, L." . "Wilcox, W. R." . . . "GB - Spojen\u00E9 kr\u00E1lovstv\u00ED Velk\u00E9 Brit\u00E1nie a Severn\u00EDho Irska" . "IL-6 and downstream JAK-dependent signaling pathways have critical roles in the pathophysiology of multiple myeloma (MM). We investigated the effects of a novel small-molecule JAK inhibitor (AZD1480) on IL-6/JAK signal transduction and its biological consequences on the human myeloma-derived cell lines U266 and Kms. 11. At low micromolar concentrations, AZD1480 blocks cell proliferation and induces apoptosis of myeloma cell lines. These biological responses to AZD1480 are associated with concomitant inhibition of phosphorylation of JAK2, STAT3 and MAPK signaling proteins. In addition, there is inhibition of expression of STAT3 target genes, particularly Cyclin D2. Examination of a wider variety of myeloma cells (RPMI 8226, OPM-2, NCI-H929, Kms. 18, MM1. S and IM-9), as well as primary myeloma cells, showed that AZD1480 has broad efficacy. In contrast, viability of normal peripheral blood (PB) mononuclear cells and CD138(+) cells derived from healthy controls was not significantly inhibited." . "RIV/00216224:14310/11:00050507!RIV12-GA0-14310___" . "P(GA301/09/0587), Z(MSM0021622430)" . "10.1038/leu.2010.289" . . "0887-6924" . "13"^^ .