Using a novel cell-based assay to profile transcriptional pathway targeting, we have identified a new functional class of thalidomide analogs with distinct and selective antileukemic activity. These agents activate nuclear factor of activated T cells (NFAT) transcriptional pathways while simultaneously repressing nuclear factor-kappaB (NF-kappaB) via a rapid intracellular amplification of react...

Arsenic trioxide (As2O3) exhibits potent antineoplastic effects and is used extensively in clinical oncology for the treatment of a subset of patients with acute myeloid leukemia (AML). Although As2O3 is known to regulate activation of several signaling cascades, the key events, accounting for its antileukemic properties, remain to be defined. We provide evidence that arsenic can directly bind ...

Tiazofurin (2-/3-i>-ribofuranosylthiazole-4-carboxamide, NSC 286193), a selective inhibitor of the activity of IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, provided in end stage leukemic patients a rapid decrease of IMP dehydrogenase activity and GTP concentration in the blast cells and a subsequent decline in blast cell count. Sixteen consecutive pati...

AKR mice with spontaneous leukemia were infused with normal serum from a variety of species. Leukemia cell destruction was produced by serum from strains of mice possessing the full spectrum of complement components, but not by serum from strains with a genetically determined deficiency of C5. Serum from guinea pigs, horses, and humans also causes destruction of leukemia cells. The antileukemic...

Abstract Background Fatty acid oxidation (FAO) provides an important source of energy to promote the growth leukemia cells. Carnitine palmitoyltransferase 1a(CPT1a), a rate-limiting enzyme essential step FAO, can facilitate cancer metabolic adaptation. Previous reports demonstrated that CPT1a acts as potential molecular target in solid tumors and hematologic disease. However, no systematic stud...

DNA is considered to be an important target for the antitumor and toxic properties of the Chloroethylnitrosoureas. Since the main target for their dose-limiting toxicity and the antileukemic efficacy is believed to be the bone marrow, we have compared the formation and subsequent removal of DNA-DNA interstrand cross-links in the bone marrow of rats which had received a single i.p. injection (10...

A study was made on serum and urinary muramidase in 56 patients with leukemia and other hematologic disorders. Serum and urinary muramidase levels prior to antileukemic therapy were elevated in monocytic leukemia, while not so increased in paramyeloblastic leukemia. In all patients with acute lymphocytic leukemia pretreatment serum enzyme activities were decreased below normal, whereas those in...