All-trans-retinoic acid (ATRA) is the drug of choice in the treatment of acute promyelocytic leukemia (APL). ATRA induces both in vitro and in vivo differentiation of APL cells into mature granulocytes. However, the molecular mechanisms involved in ATRA-dependent growth inhibition and cellular differentiation are not presently understood. The NB4 cell line, which is derived from the bone marrow...

The unique t(15;17) of acute promyelocytic leukemia (APL) fuses the PML gene with the retinoic acid receptor alpha (RAR alpha) gene. Although retinoic acid (RA) inhibits cell growth and induces differentiation in human APL cells, resistance to RA develops both in vitro and in patients. We have developed RA-resistant subclones of the human APL cell line, NB4, whose nuclear extracts display alter...

In this report we show a strong synergistic interaction between granulocyte colony-stimulating factor (G-CSF) and all-trans retinoic acid (ATRA) on the expression of leukocyte alkaline phosphatase (LAP) in freshly isolated acute promyelocytic leukemia (APL) blasts as well as in NB40 and HL-60 cell lines. The strong synergism observed in these cell types was not evident in two acute leukemia cel...

The unique t(15;17) of acute promyelocytic leukemia (APL) retinoid response elements (RAREs). This leads to a dominant negative block of transcription from RAREs that is dosefuses the PML gene with the retinoic acid receptor a (RARa) gene. Although retinoic acid (RA) inhibits cell growth and dependent and not relieved by RA. An unrearranged RARa engineered with this mutation also lost ligand bi...

Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) expression in acute promyelocytic leukemia (APL) impairs transforming growth factor beta (TGFβ) signaling, leading to cell growth advantage. Halofuginone (HF), a low-molecular-weight alkaloid that modulates TGFβ signaling, was used to treat APL cell lines and non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice subjec...

Resistance to all-trans retinoic acid (ATRA) remains a clinical problem in the treatment of acute promyelocytic leukemia (APL) and provides a model for the development of novel therapies. Molecular alterations in the ligand-binding domain (LBD) of the PML/RAR fusion gene that characterizes APL constitute one mechanism of acquired resistance to ATRA. We identified missense mutations in PML/RAR f...

The unique t(15;17) of acute promyelocytic leukemia (APL) retinoid response elements (RAREs). This leads to a dominant negative block of transcription from RAREs that is dosefuses the PML gene with the retinoic acid receptor a (RARa) gene. Although retinoic acid (RA) inhibits cell growth and dependent and not relieved by RA. An unrearranged RARa engineered with this mutation also lost ligand bi...

BACKGROUND Thrombin, the final enzyme of blood coagulation, is a multifunctional serine protease also involved in the progression of cancer. Tumor cells may activate blood coagulation proteases through the expression of procoagulant activities. However, specific information about the thrombin generation potential of malignant tissues is lacking. In this study we applied a single global coagulat...