ATM is usually rearranged in T-cell prolymphocytic leukaemia
ATM is usually rearranged in T-cell prolymphocytic leukaemia
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ATM 通常在 T 细胞幼淋巴细胞白血病中重排
作者：
M. Yuille;L. Coignet;SM Abraham;F. Yaqub;L. Luo;E. Matutes;V. Brito‐Babapulle;I. Vořechovský;M. Dyer;D. Catovsky
T-幼淋巴细胞白血病（T-PLL）是一种罕见的散发性白血病，类似于在共济失调毛细血管扩张症（A-T）患者中观察到的成熟T细胞白血病，这是一种由染色体11q23处ATM基因突变引起的隐性多系统疾病。据报道，46%的T-PLL病例中存在ATM序列突变，但一些病例在11q也存在核型异常，包括11q23。这使我们在一组8例病例中研究ATM基因座的结构，其中2例有11q23异常。正如预期的那样，在一些样品中检测到核苷酸变化。两个缓解样品为野生型。为了测试结构性病变，DNA纤维与跨越ATM基因座的四个标记的互补序列的重叠群杂交。在所有的样品中，有结构病变，并在四个样品中的两个等位基因受到影响。这为我们提出的ATM在T-PLL肿瘤发生过程中作为肿瘤抑制因子的建议提供了强有力的证据。ATM在T-PLL肿瘤发生过程中的一些额外作用是可能的，因为除了破坏两个等位基因的结构性病变之外，还存在核苷酸变化。失活的机制似乎是不寻常的，因为经常观察到一个等位基因上的多个结构损伤。
T-prolymphocytic leukaemia (T-PLL) is a rare, sporadic leukaemia similar to a mature T-cell leukaemia seen in some patients with Ataxia Telangiectasia (A-T), a recessive multisystem disorder caused by mutations of the ATM gene at chromosome 11q23. ATM sequence mutations have been reported in 46% of T-PLL cases, but some cases also have karyotypic abnormalities at 11q, including 11q23. This led us to investigate the structure of the ATM locus in a panel of eight cases, two of which had 11q23 abnormalities. As expected, nucleotide changes were detected in some samples. Two remission samples were wild type. To test for structural lesions, DNA fibres were hybridized with a contig of four labelled cosmids spanning the ATM locus. In all samples there were structural lesions and in four samples both alleles were affected. This provides strong evidence for our suggestion that ATM acts as a tumour suppressor during T-PLL tumorigenesis. Some additional role for ATM during T-PLL tumorigenesis is possible since nucleotide changes were present in addition to structural lesions disrupting both alleles. The mechanism of inactivation appeared to be unusual because multiple structural lesions on one allele were often observed.