Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mixed lineage leukemia (MLL) gene located at chromosome band 11q23 is frequently rearranged in patients with therapy-related acute monocytic leukemia who received topoisomerase II inhibitors. We have identified a novel fusion partner of MLL (FAB M5b) in a patient who developed t-AML 9 years after treatment for acute lymphoblastic leukemia (ALL). The leukemic cells had a sole karyotypic abnormality of t(3;11) (p21;q23). Screening of a genomic DNA library, prepared from leukemic cell DNA, identified rearranged clones composed of MLL and a novel gene on chromosome 3p21 (AF3p21). The AF3p21 gene encodes a protein of 722 amino acids, which contains an Src homology 3 (SH3) domain, a proline-rich domain, and a bipartite nuclear localizing signal (NLS). RNA analysis demonstrated that exon 6 of the MLL gene fused to exon 2 of the AF3p21 gene. The resulting chimeric protein consists of AT-hooks, methyltransferase, and transcription repressor domains of MLL in addition to the AF3p21 proline-rich domain and NLS but not the AF3p21 SH3 domain.
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PMID:Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage leukemia protein in a therapy-related leukemia with t(3;11) (p21;q23). 1064 23

We have identified a new mixed lineage leukemia (MLL) gene fusion partner in a patient with treatment-related acute myeloid leukemia (AML) presenting a t(2;11)(q37;q23) as the only cytogenetic abnormality. Fluorescence in situ hybridization demonstrated a rearrangement of the MLL gene and molecular genetic analyses identified a septin family gene, SEPT2, located on chromosome 2q37, as the fusion partner of MLL. RNA and DNA analyses showed the existence of an in-frame fusion of MLL exon 7 with SEPT2 exon 3, with the genomic breakpoints located in intron 7 and 2 of MLL and SEPT2, respectively. Search for DNA sequence motifs revealed the existence of two sequences with 94.4% homology with the topoisomerase II consensus cleavage site in MLL intron 7 and SEPT2 intron 2. SEPT2 is the fifth septin family gene fused with MLL, making this gene family the most frequently involved in MLL-related AML (about 10% of all known fusion partners). The protein encoded by SEPT2 is highly homologous to septins 1, 4 and 5 and is involved in the coordination of several key steps of mitosis. Further studies are warranted to understand why the septin protein family is particularly involved in the pathogenesis of MLL-associated leukemia.
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PMID:SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23). 1668 51