Several lines of investigation suggest that granulocyte colony-stimulating factor (G-CSF) augments all-trans retinoic acid (ATRA)-induced neutrophil differentiation in acute promyelocytic leukemia (APL). We sought to characterize the relationship between G-CSF- and ATRA-mediated neutrophil differentiation. We established a G-CSF receptor-transduced promyelocytic cell line, EPRO-Gr, derived from...

The NB4 promyelocytic cell line exhibits many of the characteristics of acute promyelocytic leukemia blast cells, including the translocation (15 : 17) that fuses the PML gene on chromosome 15 to the RARα gene on chromosome 17. These cells have a very high fibrinolytic capacity. In addition to a high secretion of urokinase, NB4 cells exhibit a 10-fold higher plasminogen binding capacity compare...

Acute promyelocytic leukemia (APL) is a special subtype of acute myeloid leukemia that responds to treatment with all‑trans retinoic acid and arsenic trioxide. However, severe side effects and drug resistance limit the effectiveness of these treatments. Hence, new drugs for APL are required urgently. Shikonin, an active naphthoquinone derived from the Chinese medical herb Zi Cao exerts antitumo...

All-trans retinoic acid (tRA), a naturally occurring ligand of the nuclear retinoic acid receptors (RARs), induces differentiation of leukemic cells and clinical complete remission in patients with acute promyelocytic leukemia (APL). This differentiation effect can also be seen in vitro in both fresh leukemic cells and in the unique permanent APL cell line, NB4. However, APL cells become resist...

Amifostine is used as a cytoprotective agent in cancer treatments. Amifostine protects from apoptosis in some models and has been used as hematopoiesis stimulator in myeloid malignancies. As the apoptosis induced by many antitumoral agents is mediated by p53, we studied the effect of amifostine on p53-mediated apoptosis. We used human myeloid leukemia K562 and NB4 cells expressing the temperatu...

Neutrophil elastase (NE) is a neutrophil‑derived serine proteinase with specificity for a broad range of substrates. NE has been reported to be associated with the pathogenesis of several conditions, particularly that of pulmonary diseases. Previous studies have shown that NE can cleave the pro‑myelocyte ‑ retinoic acid receptor‑alpha chimeric protein and is important for the development of acu...

Differentiation therapy based on all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) for the treatment of acute promyelocytic leukemia (APL) is complicated by the development of differentiation syndrome (DS), which can be fatal. We examined the role of HMGB1 (high-mobility group box 1) in DS using both in vitro and in vivo models. HMGB1 and the pro-inflammatory cytokines IL-1β and TNF-α w...

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 (...

The acute promyelocytic leukemia cell line NB4 was differentiated by all-trans retinoic acid (ATRA), which enhanced the superoxide-producing capacity stimulated by the chemotactic peptide and phorbol ester in this cell line. Granulocyte colony-stimulating factor (G-CSF) by itself had no effect on NB4 cells but exerted additional enhancing effects on the respiratory burst activity in the presenc...

Bactericidal/permeability-increasing protein (BPI) neutralizes the proinflammatory effects of lipopolysaccharide and is of potential clinical use in the treatment of fulminant Gram-negative infections. BPI is a cationic protein with antibacterial activity stored in azurophil (primary) granules of neutrophil granulocytes. However, the absence of BPI in patients with specific granule deficiency i...