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

Authors :: Yang J
Ikezoe T
Nishioka C
Honda G
Yokoyama A
Source :: Leukemia research [Leuk Res] 2012 May; Vol. 36 (5), pp. 625-33. Date of Electronic Publication: 2012 Feb 18.
Publication Year :: 2012
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.<br /> (Copyright Â© 2012 Elsevier Ltd. All rights reserved.)

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

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