title: NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients.
abstract: JAK2/STAT signaling promotes survival and expansion of myelodysplastic syndrome (MDS) clones, but little is known about the potential of JAK2/STAT as a therapeutic target in MDS. We investigated the effect of NS-018, a novel antagonist for JAK2, on the colony-forming ability of bone marrow mononuclear cells (BMMNCs) from high-risk MDS patients. NS-018 decreased colony-forming unit-granulocyte/macrophage (CFU-GM) colony numbers from MDS-derived BMMNCs in a dose-dependent manner, and this effect was significantly more potent than against normal BMMNCs. In addition, NS-018 suppressed the phosphorylation of STAT3 in colony-forming cells from MDS patients. Collectively, NS-018 could be a new therapeutic option for high-risk MDS.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: junkuro@koto.kpu-m.ac.jp.
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.affiliation: Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kodama
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Chinen
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimura
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Mizutani
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Nagoshi
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Nakaya
authors.affiliation: Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tamura
authors.affiliation: Department of Hematology, Kyoto Second Red Cross Hospital, Kyoto, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Naito
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012306:Risk; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects*
chemical_list: D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053614:Janus Kinase 2
keywords: CFU-GM; JAK2; Myelodysplastic syndrome; NS-018; STAT