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Hematopoiesis is a tightly regulated process resulting in the production of blood cells. Self-renewal and differentiation of hematopoietic stem cells (HSCs) are key processes in hematopoietic development. Disruption of these steps can lead to altered cell distribution and disease. To investigate the role of the nuclear factor-κB subunit RelA/p65 in the(More)
Chronic myelogenous leukemia is a malignant disease of the hematopoietic stem cell compartment, which is characterized by expression of the BCR-ABL fusion protein. Expression of BCR-ABL allows myeloid cells to grow in the absence of the growth factors interleukin-3 and granulocyte-macrophage colony-stimulating factor. The tyrosine kinase activity of BCR-ABL(More)
Elevated levels of reactive oxygen species (ROS) are found in most oncogenically transformed cells and are proposed to promote cellular transformation through mechanisms such as inhibition of phosphatases. BCR-ABL, the oncoprotein associated with the majority of chronic myeloid leukemias (CMLs), induces accumulation of intracellular ROS, causing enhanced(More)
Chronic myelogenous leukemia is a malignant disease of the hematopoietic stem cell compartment, which is characterized by expression of the BCR-ABL fusion protein. Expression of BCR-ABL allows myeloid cells to grow in the absence of the growth factors interleukin-3 and granulocyte-macrophage colony-stimulating factor. The tyrosine kinase activity of BCR-ABL(More)
Activating NOTCH1 mutations are frequent in human T-cell acute lymphoblastic leukemia (T-ALL) and Notch inhibitors (γ-secretase inhibitors [GSIs]) have produced responses in patients with relapsed, refractory disease. However, sustained responses, although reported, are uncommon, suggesting that other pathways can substitute for Notch in T-ALL. To address(More)
Trib2 is highly expressed in human T cell acute lymphoblastic leukemia (T-ALL) and is a direct transcriptional target of the oncogenic drivers Notch and TAL1. In human TAL1-driven T-ALL cell lines, Trib2 is proposed to function as an important survival factor, but there is limited information about the role of Trib2 in primary T-ALL. In this study, we(More)
Granulocytic colonies grown in culture from marrow and peripheral blood from five patients with Ph1-positive CML and heterozygous at the G-6-PD locus were analyzed for G-6-PD in order to identify CFU-C that do not arise from the CML clone. The patients had both B and A enzymes in normal tissues, but their CML clones typed as B. Whereas about 50% of colonies(More)
COP1 proteins are E3 ubiquitin ligases that regulate phototropism in plants and target transcription factors for degradation in mammals. The substrate-binding region of COP1 resides within a WD40-repeat domain that also binds to Trib proteins, which are adaptors for C/EBPα degradation. Here we report structures of the human COP1 WD40 domain in isolation,(More)
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