Thick J, Metcalfe J A, Mak Y F, Beatty D, Minegishi M, Dyer M J, Lucas G, Taylor A M
Institute for Cancer Studies, Medical School, University of Birmingham, UK.
Oncogene. 1996 Jan 18;12(2):379-86.
Patients with the recessively inherited disorder ataxia telangiectasia (A-T) have a high level of specific chromosome translocations which can be easily observed in peripheral T cells and show a greatly increased predisposition to leukaemia/lymphoma, mainly of T cell origin. Some translocation cells proliferate into a large clone and may develop into T cell prolymphocytic leukaemia (T-PLL). By the time of diagnosis of T-PLL, the clone contains many more genetic changes in the form of additional translocations. T-PLL is also seen in non-A-T individuals where expression of either TCL1 (at 14q32) or the c6.1B/MTCP1 A1 transcript (at-Xq28) has been demonstrated in just a few instances. We show here, that expression of TCL1 occurs in leukaemic T cells from A-T patients with chromosome 14 rearrangements. Expression of TCL1 also occurs in the preleukaemic clone cells of A-T patients containing the primary translocation alone. Some expression of TCL1 could also be detected in randomly selected A-T patients without large cytogenetic clones and without any evidence of leukaemic change. We also show that expression of the B1 transcript from a second gene, MTCP1, occurred at a relatively high level only in two T-PLL tumours from A-T patients with t(X;14) translocations whereas the MTCP1/A1 transcript is much more widely expressed in both tumour and non tumour cells of A-T and non-A-T individuals.
患有隐性遗传疾病共济失调毛细血管扩张症(A-T)的患者具有高水平的特定染色体易位,这些易位在外周血T细胞中很容易观察到,并且显示出患白血病/淋巴瘤的易感性大大增加,主要是T细胞起源的。一些易位细胞增殖形成一个大克隆,并可能发展为T细胞幼淋巴细胞白血病(T-PLL)。在诊断T-PLL时,该克隆包含更多以额外易位形式存在的基因变化。T-PLL也见于非A-T个体,在少数情况下已证实有TCL1(位于14q32)或c6.1B/MTCP1 A1转录本(位于Xq28)的表达。我们在此表明,TCL1的表达发生在患有14号染色体重排的A-T患者的白血病T细胞中。TCL1的表达也发生在仅含有原发性易位的A-T患者的白血病前期克隆细胞中。在随机选择的没有大的细胞遗传学克隆且没有任何白血病变化证据的A-T患者中也能检测到一些TCL1的表达。我们还表明,来自第二个基因MTCP1的B1转录本的表达仅在两名患有t(X;14)易位的A-T患者的T-PLL肿瘤中相对高水平出现,而MTCP1/A1转录本在A-T和非A-T个体的肿瘤细胞和非肿瘤细胞中表达更为广泛。