Retinoic acid is known to induce differentiation of human myeloid leukemia cells in vitro. Recently, all-trans retinoic acid has been used to induce remissions in patients with acute promyelocytic leukemia, probably through differentiation of the leukemia cells. Myeloblastin (mbn) is a protease that has been identified in the human leukemia cell line HL-60. Downregulation of this protease can i...

BACKGROUND Although standard first line treatment of acute promyelocytic leukemia is All trans retinoic acid (ATRA) and chemotherapy, some patients relapse and need a second line of treatment. Relapsed cases of promyelocytic leukemia can be salvaged with arsenic trioxide. METHODS Between May 1999 and Jan. 2010, we treated 31 relapsed cases of promyelocytic leukemia with arsenic trioxide. Thes...

Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular different...

On their own, retinoid X receptor (RXR)-selective ligands (rexinoids) are silent in retinoic acid receptor (RAR)-RXR heterodimers, and no selective rexinoid program has been described as yet in cellular systems. We report here on the rexinoid signaling capacity that triggers apoptosis of immature promyelocytic NB4 cells as a default pathway in the absence of survival factors. Rexinoid-induced a...

ABSTRACT The heat-shock response is critical for the survival of all organisms. Metastasis-associated long adenocarcinoma transcript 1 (MALAT1) a noncoding RNA localized in nuclear speckles, but its physiological role remains elusive. Here, we show that heat shock induces translocation MALAT1 to distinct body named shock-inducible RNA-containing (HiNoCo) mammalian cells. MALAT1-knockout A549 ce...

Patients with acute promyelocytic leukemia often develop bleeding diatheses during treatment. In seven patients who had this disease, the plasma level of alpha-2-plasmin inhibitor was the best predictor of severity of coagulopathy and bleeding. Clinical bleeding occurred when alpha-2-plasmin inhibitor levels measured less than 30% of normal levels. Patients with acute promyelocytic leukemia who...

Diospyros kaki Thunb. (Ebenaceae) is widely distributed in North-East Asian countries. Almost all parts of this plant have been traditionally used as medicine. Human promyelocytic leukemia cells differentiate into monocytes or granulocytes when treated with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Combination of low doses of ATRA or 1,25-dihydroxyvitamin D3 tha...

Promyelocytic leukemia protein (PML) is a major component of PML nuclear bodies (PML NBs). Fusion of promyelocytic leukemia alpha gene (PML) with retinoic acid receptor gene with the t (15;17) translocation causes disassembly of PML NBs, leading to development of acute promyelocytic leukemia. In contrast, PML overexpression as well as different morphological changes of PML NBs were described in...

Acute promyelocytic leukemia (APL) is characterized by specific chromosomal translocations, which generate fusion proteins such as promyelocytic leukemia (PML)-retinoic acid receptor (RAR) and promyelocytic leukemia zinc finger (PLZF)-RAR (X-RAR ). In this study, we have applied lac operator array systems to study the effects of X-RAR versus wild-type RAR on large-scale chromatin structure. The...