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Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow. Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic(More)
PURPOSE Characterization of an approach to identify leukemia neoantigens arising in the context of drug resistance. EXPERIMENTAL DESIGN We assessed whether leukemia neoantigens could be generated from drug-resistant mutations in BCR-ABL after imatinib relapse in patients with chronic myelogenous leukemia (CML). RESULTS We computationally predicted that(More)
Mutation in the ABL kinase domain is the principal mechanism of imatinib resistance in patients with chronic myelogenous leukemia. Many mutations favor active kinase conformations that preclude imatinib binding. Because the active forms of ABL and SRC resemble one another, we tested two dual SRC-ABL kinase inhibitors, AP23464 and PD166326, against 58(More)
PURPOSE OF REVIEW Aside from bone marrow transplantation, a definitive cure for Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) has yet to be developed. Although Imatinib, the first molecularly targeted drug developed for CML has achieved a remarkable success, the emergence of resistance to this agent mitigates the prospect of a cure(More)
BACKGROUND Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the(More)
Interferon (IFN) is effective at inducing complete remissions in patients with chronic myelogenous leukemia (CML), and evidence supports an immune mechanism. Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN consensus sequence-binding protein (ICSBP) in BCR-ABL-transformed cells and as shown previously for ICSBP, induce a(More)
Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3. Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic(More)
BACKGROUND Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. Few single-institution series have been reported. METHODS Review of MCC patients treated at our institution between 1980 and 2010. Patient, tumor, and treatment variables were analyzed to determine MCC-specific outcomes. RESULTS We identified 161 patients with MCC. There was a(More)
PURPOSE Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor, often metastatic at presentation, for which current chemotherapeutic regimens are largely ineffective. As its pathogenesis is still unknown, we hypothesized that deregulation of signaling pathways commonly activated in cancer may contribute to MCC tumorigenesis and may(More)
We examined pathological changes and relationship between body condition index (BCI) and parasitic infection in 5 species of fish, including 42 icefish Chionodraco hamatus (Channichtyidae), 2 dragonfish Cygnodraco mawsoni (Bathydraconidae), 30 emerald rock cod Trematomus bernacchii, 46 striped rock cod T. hansoni and 9 dusty rock cod T. newnesi(More)