A common Vδ2-Dδ2-Dδ3 T cell receptor gene rearrangement in precursor B acute lymphoblastic leukaemia
1991
Despite their apparent commitment to the B lymphocytic lineage, human precursor B cell acute lymphoblastic leukaemias (ALL) frequently rearrange their T cell antigen receptor (TCR) α, β and γ chain genes. Since these three genes are active sites of rearrangement in precursor B cell neoplasms, it seemed that the recently discovered fourth TCR gene, δ, might be similarly rearranged. To investigate this possibility, a series of precursor B cell leukaemias was analysed for rearrangements at the δ chain gene locus, using probes of the variable, joining, and constant regions of the δ chain gene.
The majority of precursor B cell ALLs in this series (25/32, 78%) showed rearrangement or deletion of one or more TCR δ genes. This contrasts sharply with a series of 16 mature B cell neoplasms (chronic lymphocytic leukaemia) in which no TCR δ gene rearrangements were detected.
An unusual TCR δ rearrangement, rarely observed in normal or neoplastic T cells, was seen in the majority (14/18) of precursor B cell ALLs with TCR δ rearrangements. In contrast to the utilization ov Vδ1 in T cell ALL, detailed restriction mapping of precursor B ALL revealed an incomplete rearrangement without involvement of Jδ segments. Direct genomic sequencing was performed on one example and demonstrated a nonproductive Vδ2-Dδ2-Dδ1 recombination in this precursor B ALL.
We conclude that the TCR δ chain gene is an active locus in precursor B cell neoplasia, involves an unusual type of rearrangement and provides a clonal tumour marker for diagnosis of precursor B ALL.
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