Methylation status of T-cell receptor beta-chain gene in B precursor acute lymphoblastic leukemia: correlation with hypomethylation and gene rearrangement.
Epigenetic changes may play a role in genetic alterations in cancer cells, but little is known about this phenomenon. In this study we examined the correlation between rearrangement and methylation status of the T-cell receptor (TCR) beta-chain gene in 23 patients with B precursor acute lymphoblastic leukemia (ALL). In B precursor ALL, all patients had a CCmeGG sequence in the C beta 2 region, a pattern similar to that observed in normal mature B-cells. Approximately 55% of patients with B precursor ALL exhibiting a hypomethylated CCGG sequence at the J beta 1 region showed rearrangement of this region. Furthermore, the same allele of rearranged J beta 1 always contained an unmethylated sequence in the region, although another allele without rearrangement contained methylated J beta 1. By contrast, none of the patients had a rearrangement in the J beta 1 region without hypomethylation. Therefore, rearrangement of the J beta 1 region may link to the hypomethylation status of this region. A close association between hypomethylation of the J beta 1 region may promote accessibility to a putative common recombinase to produce TCR J beta 1 rearrangement. In contrast, about 45% of patients with a hypomethylated J beta 1 did not show rearrangement in this region, thus allowing categorization of B precursor ALL patients into subtypes, according to the combination of TCR beta-chain gene rearrangement and hypomethylation status, especially in the J beta 1 region.
Tauchi
T
T
First Department of Internal Medicine, Tokyo Medical College, Japan.
Ohyashiki
J H
JH
Ohyashiki
K
K
Saito
M
M
Nakazawa
S
S
Kimura
N
N
Toyama
K
K
D002051:Burkitt Lymphoma / Q000235:genetics*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D008745:Methylation; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping
D012333:RNA, Messenger