Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most common gene fusion (up to 25%) in childhood acute lymphoblastic leukemia (ALL) is that between ETV6 and RUNX1 (previously TEL and AML1, respectively; we here use the old nomenclature, for ease of reference to the literature). We determined the incidence of TEL/AML1 translocation with reverse transcriptase polymerase chain reaction (RT-PCR) and flow-cytometric immunophenotyping of newly diagnosed pediatric acute lymphoblastic leukemia patients in Thailand. The TEL/AML1 fusion genes were cloned into plasmids and sequenced. The variant found was confirmed with restriction fragment length polymorphism (RFLP) using SphI restriction endonuclease. Of 35 ALL patients, we found an incidence of 8.6% of TEL/AML1 translocation in ALL patients (12% of B-lineage ALL), which is lower than that reported in caucasians but is similar to that reported in Japanese and Koreans. All the translocation-positive patients had B-lineage common ALL, expressing CD10+. Interestingly, the two TEL/AML1 subclones were CD20 negative, and one subclone expressed a myelocytic marker (CD33+). Two TEL/AML1 subclones from bone marrow of ALL patients were isolated and sequenced. One was a wild type and the other was a variant having A --> G substitution at nucleotide 73 from the 5' end. The substitution nucleotide was located in the AML1 region. The clinical relevance of the variant is to be investigated.
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PMID:Cloning and sequencing of ETV6/RUNX1 (TEL/AML1) variant in acute lymphoblastic leukemia. 1510 90

The recombination activating gene (RAG) is a lymphoid-specific endonuclease involved in the V(D)J recombination. It has long been proposed that mis-targeting of RAG proteins is one of the factors contributing to lymphoid chromosomal translocation bearing authentic recombination signal sequences (RSSs) in immunoglobulin (Ig) and T cell receptor (TCR) gene loci or cryptic RSSs (cRSSs). However, it is unclear whether primary sequence-dependent targeting mistake involved in the chromosomal translocation bearing no Ig/TCR gene loci is mediated by RAG proteins. Using an extrachromosomal recombination assay, we found RAG-dependent recombination in the regions dense in breakpoints within TEL and AML1 gene loci related to acute lymphoid leukemia-associated t(12;21)(p13;q22) chromosomal translocation. Sequence analyses revealed several heptamer-like sequences located in the vicinity of RAG-dependent recombination sites. By chromatin immunoprecipitation (ChIP) and ligation-mediated PCR (LM-PCR) assays, we have shown that RAG proteins bind to and cleave the TEL translocation region dense in breakpoints. These results suggest that mis-targeting of RAG proteins to cRSSs within TEL and AML1 translocation regions might be responsible for the t(12;21)(p13;q22) chromosomal translocation not bearing Ig/TCR regions.
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PMID:RAG-dependent recombination at cryptic RSSs within TEL-AML1 t(12;21)(p13;q22) chromosomal translocation region. 2102 24