Hypomethylated status, but not RAG-1, is required for T-cell receptor-beta-chain gene rearrangement in acute leukemia cells.
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.
Kawakubo
K
K
First Department of Internal Medicine, Tokyo Medical College, Japan.
Ohyashiki
J H
JH
Ohyashiki
K
K
Tauchi
T
T
Kimura
N
N
Nakazawa
S
S
Toyama
K
K
D000208:Acute Disease; D000328:Adult; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics*; D016654:Genes, RAG-1 / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008745:Methylation; D008969:Molecular Sequence Data