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BACKGROUND Aberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters. METHODS A total of 170 patients with MDS were randomized to receive either(More)
BACKGROUND Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. METHODS This phase 3, double-blind,(More)
Leukemic cells from 30% of patients with acute myeloid leukemia (AML) have an activating mutation in the FLT3 (fms-like tyrosine kinase) gene, which represents a target for drug therapy. We treated 20 patients, each with mutant FLT3 relapsed/refractory AML or high-grade myelodysplastic syndrome and not believed to be candidates for chemotherapy, with an(More)
PURPOSE Mutations leading to constitutive activation of the FMS-like tyrosine kinase 3 receptor (FLT3) occur in blasts of 30% of patients with acute myeloid leukemia (AML). Midostaurin (PKC412; N-benzoylstaurosporin) is a multitargeted tyrosine kinase inhibitor, with demonstrated activity in patients with AML/myelodysplastic syndrome (MDS) with FLT3(More)
Fms-like tyrosine kinase 3 (FLT3) receptor mutations as internal tandem duplication (ITD) or within the kinase domain are detected in up to 35% of patients with acute myeloid leukemia (AML). N-benzoyl staurosporine (PKC412), a highly effective inhibitor of mutated FLT3 receptors, has significant antileukemic efficacy in patients with FLT3-mutated AML.(More)
Lenalidomide is approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndromes (MDSs) associated with a chromosome 5q deletion with or without additional cytogenetic abnormalities. We report results of a multicenter, phase 2 trial evaluating lenalidomide therapy for transfusion-dependent(More)
Natural killer T (NKT) cells are CD1d-restricted glycolipid reactive innate lymphocytes that play an important role in protection from pathogens and tumors. Pharmacologic approaches to enhance NKT cell function will facilitate specific NKT targeting in the clinic. Here we show that lenalidomide (LEN), a novel thalidomide (Thal) analog, enhances(More)
Vemurafenib, a selective RAF inhibitor, extends survival among patients with BRAF V600E-mutant melanoma. Vemurafenib inhibits ERK signaling in BRAF V600E-mutant cells but activates ERK signaling in BRAF wild-type cells. This paradoxical activation of ERK signaling is the mechanistic basis for the development of RAS-mutant squamous-cell skin cancers in(More)
PURPOSE Epigenetic modulation of gene expression plays an important role in cancer, including leukemia. Furthermore, histone deacetylase inhibitors may induce the reexpression or repression of genes critical for normal hematopoiesis. The purpose of this study was to evaluate the toxicity, pharmacokinetic profile, and selected pharmacodynamic properties of(More)
Sodium salicylate is an inexpensive, readily available anti-inflammatory agent which inhibits NF-κB in in vitro models. We examined whether it was possible to safely achieve and maintain salicylate levels known to inhibit NF-κB in vitro in 11 patients with MDS or AML taking sodium salicylate. Most patients achieved the target blood salicylate level(More)