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T‐cell prolymphocytic leukaemia: antigen receptor gene rearrangement and a novel mode of MTCP1 B1 activation
Author(s) -
De Schouwer P. J. J. C.,
Dyer M. J. S.,
BritoBabapulle V. B.,
Matutes E.,
Catovsky D.,
Yuille M. R.
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02256.x
Subject(s) - prolymphocytic leukemia , gene rearrangement , breakpoint , microbiology and biotechnology , biology , ataxia telangiectasia , t cell receptor , exon , chromosomal translocation , southern blot , gene , germline , genetics , t cell , leukemia , immune system , dna , chronic lymphocytic leukemia , dna damage
T‐cell prolymphocytic leukaemia (T‐PLL) is a sporadic, mature T‐cell disorder in which there is usually an aberrant T‐cell receptor alpha ( TCRA ) rearrangement that activates the TCL1 or MTCP1 ‐B1 oncogenes. As mutations of the Ataxia Telangiectasia (A‐T) gene, ATM , are frequent in T‐PLL and as ATM seems to act as a tumour suppressor through a mechanism involving V(D)J recombination, we examined V(D)J recombination in T‐PLL. Using Southern blotting and the polymerase chain reaction, two of 60 TCRG coding joints were abnormal. In all cases, both TCRD alleles were deleted, IGH was germline, and patterns of TCRB and TCRA rearrangement were normal. However, in a case harbouring t(X;7)(q28;q35), we identified TCRB segment Jβ2·7 juxtaposed to MTCP1 exon 1. This is the first time that TCRB has been implicated in MTCP1 B1 activation. The structure of the breakpoint supports a model in which translocation activates a cryptic MTCP1 promoter. This analysis of V(D)J recombination is consistent with it being a variable that is independent of ATM in T‐PLL.