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Methylation Status of T-Cell Receptor ß-Chain Gene in B Precursor Acute Lymphoblastic Leukemia: Correlation with Hypomethylation and Gene Rearrangement¹

First Department of Internal Medicine, Tokyo Medical College, Tokyo [T. T., J. H. O., K. O., K. T.]; Department of Pediatrics, School of Medicine, Keio University, Tokyo [M. S.]; Department of Pediatrics, Yamanashi Medical School, Yamanashi [S. N.]; and the First Department of Internal Medicine, Fukuoka University, Fukuoka [N. K.], Japan

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) ß-chain gene in 23 patients with B precursor acute lymphoblastic leukemia (ALL). In B precursor ALL, all patients had a CC^meGG sequence in the Cß2 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 Jß1 region showed rearrangement of this region. Furthermore, the same allele of rearranged Jß1 always contained an unmethylated sequence in the region, although another allele without rearrangement contained methylated Jß1. By contrast, none of the patients had a rearrangement in the Jß1 region without hypomethylation. Therefore, rearrangement of the Jß1 region may link to the hypomethylation status of this region. A close association between hypomethylation and rearrangement of the TCR ß-chain gene indicates that hypomethylation of the Jß1 region may promote accessibility to a putative common recombinase to produce TCR Jß1 rearrangement. In contrast, about 45% of patients with a hypomethylated Jß1 did not show rearrangement in this region, thus allowing categorization of B precursor ALL patients into subtypes, according to the combination of TCR ß-chain gene rearrangement and hypomethylation status, especially in the Jß1 region.

¹ Supported in part by a Grant-in-Aid for General Scientific Research from the Ministry of Education, Science, and Culture (02671137) and the Uehara Memorial Foundation.

² To whom requests for reprints should be addressed, at First Department of Internal Medicine, Tokyo Medical College, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160, Japan.

Received 12/10/90. Accepted 3/22/91.