K. Kawakubo et al., HYPOMETHYLATED STATUS, BUT NOT RAG-1, IS REQUIRED FOR T-CELL RECEPTOR-BETA-CHAIN GENE REARRANGEMENT IN ACUTE-LEUKEMIA CELLS, Cancer genetics and cytogenetics, 78(1), 1994, pp. 40-45
We studied the relation between the level of recombinase activating ge
ne (RAG-1) and the methylation status of T-cell receptor (TCR)beta-cha
in gene in TCR-beta rearrangement in acute leukemias, including 21 pat
ients 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 hypom
ethylated cytosine-cytosine-guanine-guanine (CCGG) sequences within ei
ther the TCR-J beta 1 or TCR-J beta 1 regions. Moreover, all B-precurs
or ALL patients with TCR-beta rearrangement had hypomethylated TCR-bet
a with or without the presence of RAG-1 activity detectable by reverse
transcript-polymerase chain reaction, whereas none of the AML patient
s with TCR-beta rearrangement and hypomethylated TCR-beta had detectab
le RAG-1 activity Some ALL patients had hypomethylated TCR-beta and RA
G-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 correl
ation between the hypomethylation status of the TCR-beta and its rearr
angements, but some unknown blockage factor for this association exist
s in B-precursor ALL patients with specific chromosomal translocations
.