1. Academic Validation
  2. NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients

NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients

  • Leuk Res. 2014 May;38(5):619-24. doi: 10.1016/j.leukres.2014.03.001.
Junya Kuroda 1 Ayumi Kodama 2 Yoshiaki Chinen 3 Yuji Shimura 3 Shinsuke Mizutani 3 Hisao Nagoshi 3 Tsutomu Kobayashi 3 Yosuke Matsumoto 3 Yohei Nakaya 2 Ayako Tamura 2 Yutaka Kobayashi 4 Haruna Naito 2 Masafumi Taniwaki 3
Affiliations

Affiliations

  • 1 Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: junkuro@koto.kpu-m.ac.jp.
  • 2 Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan.
  • 3 Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • 4 Department of Hematology, Kyoto Second Red Cross Hospital, Kyoto, Japan.
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.

Keywords

CFU-GM; JAK2; Myelodysplastic syndrome; NS-018; STAT.

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