Identification and characterization of genomic target sites for MLL fusion proteins
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Molecular characterization of the MLL-SEPT6 fusion gene in acute myeloid leukemia: identification of novel fusion transcripts and cloning of genomic breakpoint junctions.
One of the MLL fusion partners in leukemia is the SEPT6 gene, which belongs to the evolutionarily conserved family of genes of septins. In this work we aimed to characterize at both the RNA and DNA levels three acute myeloid leukemias with cytogenetic evidence of a rearrangement between 11q23 and Xq24. Molecular analysis led to the identification of several MLL-SEPT6 fusion transcripts in all c...
متن کاملThe MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group.
MLL translocations in adult B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) are largely restricted to the immature CD10(-) immunophenotypes. MLL-AF4 is known to be the most frequent fusion transcript, but the exact frequencies of MLL aberrations in CD10(-) adult BCP-ALL are unknown. We present a genetic characterization of 184 BCR-ABL(-) CD10(-) adult ALL cases (156 cyIg(-), 28 cyIg(+...
متن کاملBinding to nonmethylated CpG DNA is essential for target recognition, transactivation, and myeloid transformation by an MLL oncoprotein.
The MLL gene is a frequent target for leukemia-associated chromosomal translocations that generate dominant-acting chimeric oncoproteins. These invariably contain the amino-terminal 1,400 residues of MLL fused with one of a variety of over 30 distinct nuclear or cytoplasmic partner proteins. Despite the consistent inclusion of the MLL amino-terminal region in leukemia oncoproteins, little is kn...
متن کاملHistone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia.
Mixed-lineage leukemia (MLL) fusions are potent oncogenes that initiate aggressive forms of acute leukemia. As aberrant transcriptional regulators, MLL-fusion proteins alter gene expression in hematopoietic cells through interactions with the histone H3 lysine 79 (H3K79) methyltransferase DOT1L. Notably, interference with MLL-fusion cofactors like DOT1L is an emerging therapeutic strategy in th...
متن کاملIdentification and characterization of EBP, a novel EEN binding protein that inhibits Ras signaling and is recruited into the nucleus by the MLL-EEN fusion protein.
The chimeric MLL-EEN fusion protein is created as a result of chromosomal translocation t(11;19)(q23;p13). EEN, an Src homology 3 (SH3) domain-containing protein in the endophilin family, has been implicated in endocytosis, although little is known about its role in leukemogenesis mediated by the MLL-EEN fusion protein. In this study, we have identified and characterized EBP, a novel EEN bindin...
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تاریخ انتشار 2006