Induction of Tissue Factor by Interleukin-2 in Acute Myelogenous Leukemia (AML) Cells

Abstract

We investigated the induction of tissue factor by lymphokines in human monoblastic leukemia cell lines (U937) and leukemic cells from AML (acute myelogenous leukemia) patients. After incubation for 24 h, IL-2 enhanced the intracellular tissue factor 15-fold with U937 cells, and GM-CSF enhanced it 6-fold. In contrast, other lymphokines, such as IL-1-alpha, IL-1-beta, IL-3, IL-4 and G-CSF, did not affect the activity of tissue factor. The leukemic blasts, depleted of T-lymphocytes, taken from five out of 16 AML patients showed a 2.5-14-fold increase in the activity of tissue factor per cell following incubation with 200 u/ml of IL-2 for 72 h. The IL-2 induced tissue factor activity more markedly than GM-CSF. Tissue factor stimulation by IL-2 did not correlate with the expression of the IL-2 receptor, Tac, but correlated well with FAB classification of AML cells. IL-2 responders were found in M4 and M5 subtypes only, but not all M4/M5 leukemias responded to IL-2. These findings indicate that IL-2 can mediate the tissue factor induction in the monocytic type of AML and the effect is not mediated by Tac receptors. This may shed a new light on our understanding of hypercoagulability in acute monoblastic leukemia.

Therapeutic Antibody-Like Immunoconjugates against Tissue Factor with the Potential to Treat Angiogenesis-Dependent as Well as Macrophage-Associated Human Diseases

“…ALL is the most common childhood malignancy and the second most common adult leukemia and AML is the second most common childhood malignancy. It was reported that TF is expressed on the human leukemic cell lines HL-60 [72,73,79,85,86], Molt-4 [87], THP-1 [11,87] and on leukemic cells from patients with AML [73,74,75,76,77,78] and ALL [79,80]. TF is not expressed on the normal peripheral mononuclear cells unless stimulated by endotoxin or other cytokines [72], nor on myeloid precursor cells [75].…”

Tissue factor as a tumor procoagulant

“…26]. Tanaka and Kishi demonstrated that IL-2 increased the TF activity by 2.5 to 14-fold in leukemic blast cells, depleted of T-lymphocytes, taken from patients with acute myelogenous leukemia [84]. Recently, Stem and colleagues [85] identified a tumor-derived mediator (meth A) in murine methylcholantherene A fibrosarcoma cells.…”

Factor VII-Targeted Photodynamic Therapy for Breast Cancer and Its Therapeutic Potential for Other Solid Cancers and Leukemia

“…If untreated, death usually occurs within 6 months in most cases. It was reported that TF is expressed on the human leukemic HL-60 (Freeburn et al, 1995;Kubota et al, 1991;Rickles et al, 1995;Tanaka et al, 1989), Molt-4 (Tanaka, 1989), THP-1 (Tanaka, 1989) cell lines , and on leukemic cells from patients with AML (Andoh et al, 1987;Bauer et al, 1989;Nakasaki et al, 2000b;Tanaka et al, 1989;Tanaka and Kishi, 1990;Tanaka and Yamanishi, 1993) and ALL (Kubota et al, 1991;Nakasaki et al, 2000a). TF is not expressed on the normal peripheral mononuclear cells unless stimulated by endotoxin or other cytokines (Rickles et al, 1995), nor on myeloid precursor cells (Bauer et al, 1989).…”