ABNORMALITIES IN T-CELL RECEPTOR LOCUS AND T-CELL LEUKEMIA

位于染色体14q11.2的T细胞受体(TCR)α/Delta基因座与多种易位有关，如t(8；14)(q24；q11)、t(14；14)(q11；q32)、inv(14)(q11；32)、t(11；14)(q13；q11)、t(11；14)(p15；q11)、t(10；14)(q23；q11)、t(1；14)(p32；q11)。这些断点特别发生在TCRα/Delta基因的JDelta、Jpha或Dalpha区域内。然而，尽管14q11.2区易位频繁发生，但尚未有直接涉及TCRα/Delta基因座的成人T细胞白血病(ATL)的报道。在研究TCRα/Delta基因座在ATL中受累的第一步中，我们分离到了13BAC和158个粘粒克隆，它们覆盖了覆盖整个TCRα/Delta基因座超过1Mb的区域。我们发现在整个TCRα/Delta基因座上有53个Valpha片段和3个VDelta片段。此外，我们将DeltaRec基因座定位在Valpha19.1和Vdelta2.1之间，这些发现表明，在α/β阳性T细胞分化过程中，DeltaRec和Pseud Jpha基因座之间的重新定位将导致Vdelta2.1-DDelta-JDelta-CDelta-Vdelta3.1区域的缺失。通过使用这些BAC克隆作为探针，我们发现在1例携带染色体异常inv(14)(Q11q32)和del(14)(Q11q32)的ATL患者的TCRα/Delta基因座内确实发生了易位。

The molecular involvement of T-cell Receptor (TCR) alpha/delta locus at chromosome 14q11.2 in a number of translocations such as t (8 ; 14) (q24 ; q11), t (14 ; 14) (q11 ; q32), inv (14) (q11 ; 32), t (11 ; 14) (q13 ; q11), t (11 ; 14) (p15 ; q11), t(10 ; 14) (q23 ; q11), an t (1 ; 14) (p32 ; q11) has been described in the HTLV-I-begative T-cell malignancies. Those breakpoints specifically occur within the Jdelta, Jalpha or Dalpha region of the TCR alpha/delta locus. However, there is no report which indicates the direct involvement of TCR alpha/delta locus adult T-cell leukemia (ATL) despite the fact of frequent occurrence of translocations at 14q11.2 region. At the first step to characterize the molicular involvement of TCR alpha/delta locus in ATL cases, we isolated 13BAC and 158 cosmid clones which cover more than 1Mb of region spanning entire TCR alpha/delta locus. We found there are 53 Valpha segment and 3 Vdelta segment in the entire TCR alpha/delta locus. Furthemore We localized the deltaRec locus in between Valpha19.1 and Vdelta2.1 and these findings suggest that the rearrngement between deltaRec and pseud Jalpha locus will cause the deltetion of Vdelta2.1-Ddelta-Jdelta-Cdelta-Vdelta3.1 region during the differentation of alpha/beta positive T-cells. By using those BAC clones as probes, we found that the translocation does occur within TCR alpha/delta locus in a case of ATL patient carrying chromosome abnormalities inv(14) (q11q32) and del (14) (q11q32).