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The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) regulates a number of myeloid cell-specific genes. To delineate the role of C/EBPalpha in human granulopoiesis, we studied its expression and function in human primary cells and bipotential (granulocytic/monocytic) myeloid cell lines. We show that the expression of C/EBPalpha(More)
Mol (complement receptor type 3, CR3; CDllb/CD18) is an adhesion-promoting human leuko-cyte surface membrane heterodimer (alpha subunit 155 kD [CDllb] noncovalently linked to a beta subunit of 95 kD [CDI8]). The complete amino acid sequence deduced from cDNA of the human alpha subunit is reported. The protein consists of 1,136 amino acids with a long(More)
The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. In particular, the expression of PU.1 in hematopoietic stem cells (HSCs) could simply represent "priming" of genes related to downstream myelolymphoid lineages. By using a conditional PU.1 knock-out model, we here show(More)
The lineage-specific transcription factors GATA-1 and PU.1 can physically interact to inhibit each other's function, but the mechanism of repression of GATA-1 function by PU.1 has not been elucidated. Both the N terminus and the C terminus of PU.1 can physically interact with the C-terminal zinc finger of GATA-1. It is demonstrated that the PU.1 N terminus,(More)
Acute promyelocytic leukemia (APL) is characterized by a block in differentiation and accumulation of promyelocytes in the bone marrow and blood. The majority of APL patients harbor the t(15:17) translocation leading to expression of the fusion protein promyelocytic-retinoic acid receptor alpha. Treatment with retinoic acid leads to degradation of(More)
OBJECTIVE Hepatocellular carcinoma (HCC) is a heterogeneous tumour displaying a complex variety of genetic and epigenetic changes. In human cancers, aberrant post-transcriptional modifications, such as alternative splicing and RNA editing, may lead to tumour specific transcriptome diversity. DESIGN By utilising large scale transcriptome sequencing of(More)
Several transcription factors have been implicated as playing a role in myelopoiesis. PU.1, an ets-family transcription factor, is required for the development of myeloid and lymphoid lineages, whereas the transcription factor CCAAT-enhancer binding protein family member C/EBPalpha is essential for granulocyte development. We present here the first evidence(More)
To develop murine models of leukemogenesis, a series of transgenic mice expressing BCR-ABL in different hematopoietic cell subsets was generated. Here we describe targeted expression of P210 BCR-ABL in stem and progenitor cells of murine bone marrow using the tet-off system. The transactivator protein tTA was placed under the control of the murine stem cell(More)
Activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain determine responsiveness to EGFR tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer (NSCLC). The modulation of transcriptional pathways by mutant EGFR signaling is not fully understood. Previously, we and others identified a single base(More)