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
  • 1. Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: [email protected].
  • 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.
PMID: 24679585 DOI: 10.1016/j.leukres.2014.03.001
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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