Abstract
Idarubicin (IDR), cytarabine (AraC), and tamibarotene (Am80) are effective for treatment of acute myeloid leukemia (AML). In acute leukemia, the incidence of venous thromboembolism or disseminated intravascular coagulation is associated with induction chemotherapy. Procoagulant effects of IDR, AraC, and Am80 were investigated in a vascular endothelial cell line EAhy926 and AML cell lines HL60 (AML M2), NB4 (AML M3, APL), and U937 (AML M5), focusing on tissue factor (TF), phosphatidylserine (PS), and thrombomodulin (TM). IDR induced procoagulant activity on the surface of vascular endothelial and AML cell lines. Expression of TF antigen, TM antigen, and PS were induced by IDR on the surface of each cell line, whereas expression of TF and TM mRNAs were unchanged. Conversely, Am80 decreased TF exposure and procoagulant activity, and increased TM exposure on NB4 cells. In NB4 cells, we observed downregulation of TF mRNA and upregulation of TM mRNA. These data suggest IDR may induce procoagulant activity in vessels by apoptosis through PS exposure and/or TF expression on vascular endothelial and AML cell lines. Am80 may suppress blood coagulation through downregulation of TF expression and induction of TM expression. Our methods could be useful to investigate changes in procoagulant activity induced by antineoplastic drugs.
Highlights
Acute myeloid leukemia (AML) is a type of cancer that affects blood and bone marrow
After treatment with IDR for 8 or 24 h, procoagulant activity (PCA) was increased on vascular endothelial and AML cells depending on the concentration
The levels of tissue factor (TF) and TM mRNAs in all cell lines hardly changed. These results suggest that IDR causes apoptosis and changes the structure of the cell membrane, leading to exposure of TF and TM on cells
Summary
Acute myeloid leukemia (AML) is a type of cancer that affects blood and bone marrow. Acute promyelocytic leukemia (APL) is a highly curable subtype of AML characterized by a unique chromosomal translocation, t(15;17), which results in formation of the PML-RARα protein. A standard form of induction therapy for AML consists of cytarabine (AraC) administered by continuous infusion for 7 days, which is combined with an anthracyclin, such as idarubicin (IDR), administered. Main treatments for APL include vitamin A derivative all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. ATRA is effective for the treatment of APL with a specific differentiating action, but it has several major limitations, one of which is rapid development of resistance [4]. Am80 was expected to have therapeutic effectiveness in patients with ATRAresistant APL [5], and it was approved for treatment of refractory and relapsed APL in Japan in 2005
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