BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia.
The majority of acute promyelocytic leukemia (APL) cases are characterized by the presence of a promyelocytic leukemia-retinoic acid receptor alpha(RARA) fusion gene. In a small subset, RARA is fused to a different partner, usually involved in regulating cell growth and differentiation. Here, we identified a novel RARA fusion transcript, BCOR-RARA, ... in a t(X;17)(p11;q12) variant of APL with unique morphologic features, including rectangular and round cytoplasmic inclusion bodies. Although the patient was clinically responsive to all-trans retinoic acid, several relapses occurred with standard chemotherapy and all-trans retinoic acid. BCOR is a transcriptional corepressor through the proto-oncoprotein, BCL6, recruiting histone deacetylases and polycomb repressive complex 1 components. BCOR-RARA was found to possess common features with other RARA fusion proteins. These included: (1) the same break point in RARA cDNA; (2) self-association; (3) retinoid X receptor alpha is necessary for BCOR-RARA to associate with the RARA responsive element; (4) action in a dominant-negative manner on RARA transcriptional activation; and (5) aberrant subcellular relocalization. It should be noted that there was no intact BCOR found in the 45,-Y,t(X;17)(p11;q12) APL cells because they featured only a rearranged X chromosome. These results highlight essential features of pathogenesis in APL in more detail. BCOR appears to be involved not only in human congenital diseases, but also in a human cancer.
Mesh Terms:
Base Sequence, Cell Line, Tumor, Chromosomes, Human, Pair 17, Chromosomes, Human, X, Cloning, Molecular, DNA-Binding Proteins, Genes, Dominant, Humans, Leukemia, Promyelocytic, Acute, Male, Middle Aged, Molecular Sequence Data, Oncogene Proteins, Fusion, Protein Binding, Protein Transport, Proto-Oncogene Proteins, RNA, Messenger, Receptors, Retinoic Acid, Repressor Proteins, Response Elements, Subcellular Fractions, Transcriptional Activation, Translocation, Genetic, Tretinoin
Base Sequence, Cell Line, Tumor, Chromosomes, Human, Pair 17, Chromosomes, Human, X, Cloning, Molecular, DNA-Binding Proteins, Genes, Dominant, Humans, Leukemia, Promyelocytic, Acute, Male, Middle Aged, Molecular Sequence Data, Oncogene Proteins, Fusion, Protein Binding, Protein Transport, Proto-Oncogene Proteins, RNA, Messenger, Receptors, Retinoic Acid, Repressor Proteins, Response Elements, Subcellular Fractions, Transcriptional Activation, Translocation, Genetic, Tretinoin
Blood
Date: Nov. 18, 2010
PubMed ID: 20807888
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