Low concentrations of As(2)O(3) (</=1 micromol/L) induce long-lasting remission in patients with acute promyelocytic leukemia (APL) without significant myelosuppressive side effects. Several groups, including ours, have shown that 0.5 to 1 micromol/L As(2)O(3) induces apoptosis in APL-derived NB4 cells, whereas other leukemic cells are resistant to As(2)O(3) or undergo apoptosis only in respons...

The present study assessed the mechanism underlying the effect of sorafenib on the proliferation and apoptosis of the acute promyelocytic leukemia (APL) cell line NB4. NB4 cells were treated with different concentrations of sorafenib (0, 1.5, 3, 6, and 12 µM) for 24, 48 and 72 h. Cell proliferation, cell cycle, and apoptosis were analyzed using an MTT assay and flow cytometry analysis, respecti...

Retinoic acid inducible gene I (RIG‑I) is upregulated during all‑trans retinoic acid (ATRA)‑induced terminal granulocytic differentiation of NB4 acute promyelocytic leukemia (APL) cells. However, the function and mechanism of RIG‑I in NB4 cells remains to be fully elucidated. In the present study, lentivirus‑mediated RIG‑I‑knockdown was used to investigate the proliferation, cell cycle and apop...

All-trans retinoic acid (tRA) and arsenic trioxide (As(2)O(3)) induce non-cross-resistant complete clinical remission in patients with acute promyelocytic leukemia with t(15;17) translocation and target PML-RARalpha, the leukemogenic protein, by different pathways suggesting a possible therapeutic synergism. To evaluate this possibility, this study examined the effect of As(2)O(3) on tRA-induce...

Since arsenic trioxide (As3+) has been successfully used in the treatment of acute promyelocytic leukemia (APL), its adverse effects on patients have been problematic and required a solution. Considering the good therapeutic potency and low toxicity of tetraarsenictetrasulfide (As4S4) in the treatment of APL, we investigated the effects of combining As4S4 and As3+ on the apoptosis and different...

Promyelocyte leukemia‑retinoic acid receptor α (PML‑RARα) is known as a fusion gene of acute promyelocytic leukemia (APL). Previous studies have reported that neutrophil elastase (NE) cleaves PML‑RARα in early myeloid cells, which leads to the removal of the nuclear localization signal (NLS) in PML and increases the incidence of APL. The resultant PML without the NLS is termed PML(NLS‑). The ai...

Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid contained in a variety of plant species, exhibits broad biological properties, including anticancer effects. Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia. APL has a unique and specific chromosomal aberration, t(15;17), which results in the formation of a fusion gene and protein PML/RARα, wh...

Translocation of genes into the pericentromeric heterochromatin occurs during cellular differentiation and leads to a long-term silencing of these genes. Consequently, a structural remodelling of this heterochromatin compartment is observed during differentiation but this remains to be defined from a topological point of view. In a previous study, we analysed the three-dimensional (3D) distribu...