title: Thrombomodulin-induced differentiation of acute myelomonocytic leukemia cells via JNK signaling.
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.
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ikezoe
authors.forename: Chie
authors.initials: C
authors.lastname: Nishioka
authors.forename: Goichi
authors.initials: G
authors.lastname: Honda
authors.forename: Akihito
authors.initials: A
authors.lastname: Yokoyama
mesh_terms: D002117:Calcitriol / Q000494:pharmacology; D002453:Cell Cycle; D002454:Cell Differentiation; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D018167:Receptors, Calcitriol / Q000032:analysis; D018180:Thrombomodulin / Q000502:physiology*
chemical_list: D018167:Receptors, Calcitriol; D018180:Thrombomodulin; D066246:ErbB Receptors; D048031:JNK Mitogen-Activated Protein Kinases; D002117:Calcitriol