2. Academic Validation
  3. Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma

Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma

  • Leukemia. 2015 Jan;29(1):207-17. doi: 10.1038/leu.2014.147.
M Hiasa 1,  J Teramachi 2,  A Oda 3,  R Amachi 4,  T Harada 3,  S Nakamura 3,  H Miki 3,  S Fujii 3,  K Kagawa 3,  K Watanabe 4,  I Endo 3,  Y Kuroda 5,  T Yoneda 6,  D Tsuji 7,  M Nakao 8,  E Tanaka 4,  K Hamada 9,  S Sano 8,  K Itoh 7,  T Matsumoto 3,  M Abe 3
Affiliations

Affiliations

  • 1 1] Department of Medicine and Bioregulatory Sciences, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan [2] Department of Biomaterials and Bioengineering, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan [3] Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
  • 2 Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
  • 3 Department of Medicine and Bioregulatory Sciences, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
  • 4 Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
  • 5 Department of Hematology and Oncology, RIRBM, Hiroshima University, Hiroshima, Japan.
  • 6 Department of Medicine, Hematology Oncology, Indiana University, Indianapolis, IN, USA.
  • 7 Department of Medicinal Biotechnology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
  • 8 Department of Molecular Medicinal Chemistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
  • 9 Department of Biomaterials and Bioengineering, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
PMID: 24787487 DOI: 10.1038/leu.2014.147
Abstract

Pim-2 kinase is overexpressed in multiple myeloma (MM) cells to enhance their growth and survival, and regarded as a novel therapeutic target in MM. However, the impact of Pim-2 inhibition on bone disease in MM remains unknown. We demonstrated here that Pim-2 expression was also upregulated in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells in the presence of cytokines known as the inhibitors of osteoblastogenesis in MM, including interleukin-3 (IL-3), IL-7, tumor necrosis factor-α, Transforming Growth Factor-β (TGF-β) and Activin A, as well as MM cell conditioned media. The enforced expression of Pim-2 abrogated in vitro osteoblastogenesis by BMP-2, which suggested Pim-2 as a negative regulator for osteoblastogenesis. Treatment with Pim-2 short-interference RNA as well as the Pim Inhibitor SMI-16a successfully restored osteoblastogenesis suppressed by all the above inhibitory factors and MM cells. The SMI-16a treatment potentiated BMP-2-mediated anabolic signaling while suppressing TGF-β signaling. Furthermore, treatment with the newly synthesized thiazolidine-2,4-dione congener, 12a-OH, as well as its prototypic SMI-16a effectively prevented bone destruction while suppressing MM tumor growth in MM animal models. Thus, Pim-2 may have a pivotal role in tumor progression and bone loss in MM, and Pim-2 inhibition may become an important therapeutic strategy to target the MM cell-bone marrow interaction.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-101947
    ≥98.0%, Pim Kinase Inhibitor
    Pim