Thrombomodulin-induced differentiation of acute myelomonocytic leukemia cells via JNK signaling

Leuk Res. 2012 May;36(5):625-33. doi: 10.1016/j.leukres.2012.01.019. Epub 2012 Feb 18.

Abstract

We found recombinant human soluble thrombomodulin (rTM) induced growth arrest and differentiation of THP-1 cells by activating JNK/c-Jun signaling. Further activation of JNK by 1,25-(OH)(2)D(3) significantly enhanced rTM-mediated growth arrest and differentiation of THP-1 cells. Importantly, forced expression of domains 1, 2 and 3 of TM (TMD123) induced growth arrest and differentiation of leukemia cells freshly isolated from individuals with AMLs of M4/M5-French-American-British classification subtypes, but not those with less advanced AML. Further studies indicated that the epidermal growth factor-like domain of TM was critical for the anti-leukemia effects of TM and these effects were independent of protein C activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcitriol / pharmacology
  • Cell Cycle
  • Cell Differentiation
  • ErbB Receptors / physiology
  • Humans
  • JNK Mitogen-Activated Protein Kinases / physiology*
  • Leukemia, Myelomonocytic, Acute / drug therapy
  • Leukemia, Myelomonocytic, Acute / pathology*
  • MAP Kinase Signaling System / physiology*
  • Receptors, Calcitriol / analysis
  • Thrombomodulin / physiology*

Substances

  • Receptors, Calcitriol
  • Thrombomodulin
  • ErbB Receptors
  • JNK Mitogen-Activated Protein Kinases
  • Calcitriol