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BACKGROUND In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial. DESIGN AND METHODS Peripheral blood and bone marrow samples were collected during(More)
PURPOSE The clinical relevance of targeting the RAS/RAF/MEK/ERK pathway, activated in 70% to 80% of patients with acute myelogenous leukemia (AML), is unknown. EXPERIMENTAL DESIGN Selumetinib is an oral small-molecule inhibitor of MAP-ERK kinase (MEK)-1/2. Forty-seven patients with relapsed/refractory AML or 60 years old or more with untreated AML were(More)
Mutations in the all-trans retinoic acid (ATRA)-targeted ligand binding domain of PML-RARα (PRα/LBD+) have been implicated in the passive selection of ATRA-resistant acute promyelocytic leukemia clones leading to disease relapse. Among 45 relapse patients from the ATRA/chemotherapy arm of intergroup protocol C9710, 18 patients harbored PRα/LBD+ (40%), 7 of(More)
6521 Background: We hypothesized that targeting two mechanisms of epigenetic silencing with a potent HDAC inhibitor BEL plus the DNA methyltransferase inhibitor AZC would be additive or synergistic with regard to transcriptional de-repression and up-regulation of specific target genes Methods: Part 1 of the study was a dose escalation phase to establish the(More)
6546 Background: MEK/MAPK and PI3K/Akt pathways have been demonstrated to be constitutively activated in the majority of AML patients and associated with poor prognosis, but inhibition of single pathway has only demonstrated modest clinical activity. METHODS The current study evaluated the efficacy of combination of orally available inhibitors to MEK(More)
Purpose: The clinical relevance of targeting the RAS/RAF/MEK/ERK pathway, activated in 70% to 80% of patients with acute myelogenous leukemia (AML), is unknown. Experimental Design: Selumetinib is an oral small-molecule inhibitor of MAP–ERK kinase (MEK)-1/2. Forty-seven patientswith relapsed/refractory AMLor 60 years old ormorewith untreatedAMLwere enrolled(More)
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