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

• Published in: Leukemia research Vol. 38; no. 5; pp. 619 - 624
• Main Authors: Kuroda, Junya, Kodama, Ayumi, Chinen, Yoshiaki, Shimura, Yuji, Mizutani, Shinsuke, Nagoshi, Hisao, Kobayashi, Tsutomu, Matsumoto, Yosuke, Nakaya, Yohei, Tamura, Ayako, Kobayashi, Yutaka, Naito, Haruna, Taniwaki, Masafumi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2014
• Subjects: Aged; Aged, 80 and over; Bone Marrow Cells - physiology; CFU-GM; Female; Hematology, Oncology and Palliative Medicine; Humans; JAK2; Janus Kinase 2 - antagonists & inhibitors; Male; Middle Aged; Myelodysplastic syndrome; Myelodysplastic Syndromes - drug therapy; NS-018; Protein Kinase Inhibitors - pharmacology; Risk; STAT; STAT3 Transcription Factor - metabolism; Stem Cells - drug effects; STAT; JAK2; Myelodysplastic syndrome; CFU-GM; NS-018
• ISSN: 0145-2126; 1873-5835
• 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.