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Hypomethylated status, but not RAG-1, is required for T-cell receptor-beta-chain gene rearrangement in acute leukemia cells.

Abstract
We studied the relation between the level of recombinase activating gene (RAG-1) and the methylation status of T-cell receptor (TCR)-beta-chain gene in TCR-beta rearrangement in acute leukemias, including 21 patients with B-precursor acute lymphoblastic leukemia (ALL) and 23 with acute myeloid leukemia (AML). The rearrangement of the TCR beta-chain gene in acute leukemia always occurs at the allele that contains hypomethylated cytosine-cytosine- guanine-guanine (CCGG) sequences within either the TCR-J beta 1 or TCR-J beta 2 regions. Moreover, all B-precursor ALL patients with TCR-beta rearrangement had hypomethylated TCR-beta with or without the presence of RAG-1 activity detectable by reverse transcript-polymerase chain reaction, whereas none of the AML patients with TCR-beta rearrangement and hypomethylated TCR-beta had detectable RAG-1 activity. Some ALL patients had hypomethylated TCR-beta and RAG-1 activity without TCR-beta rearrangement, and most of them showed t(4;11)(q21;q23) or t(9;22)(q34;q11). These results indicate a correlation between the hypomethylation status of the TCR-beta and its rearrangements, but some unknown blockage factor for this association exists in B-precursor ALL patients with specific chromosomal translocations.
AuthorsK Kawakubo, J H Ohyashiki, K Ohyashiki, T Tauchi, N Kimura, S Nakazawa, K Toyama
JournalCancer genetics and cytogenetics (Cancer Genet Cytogenet) Vol. 78 Issue 1 Pg. 40-5 (Nov 1994) ISSN: 0165-4608 [Print] United States
PMID7987804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Topics
  • Acute Disease
  • Adult
  • Base Sequence
  • Burkitt Lymphoma (genetics)
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor (genetics)
  • Genes, RAG-1 (genetics)
  • Humans
  • Leukemia, Myeloid, Acute (genetics)
  • Methylation
  • Molecular Sequence Data

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