Yuille M A, Coignet L J, Abraham S M, Yaqub F, Luo L, Matutes E, Brito-Babapulle V, Vorechovský I, Dyer M J, Catovsky D
Academic Department of Haematology and Cytogenetics, Institute of Cancer Research-Royal Marsden Hospital NHS Trust, London, UK.
Oncogene. 1998 Feb 12;16(6):789-96. doi: 10.1038/sj.onc.1201603.
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.
T 原淋巴细胞白血病（T-PLL）是一种罕见的散发性白血病，类似于某些共济失调毛细血管扩张症（A-T）患者中出现的成熟 T 细胞白血病，A-T 是一种由 11q23 染色体上 ATM 基因突变引起的隐性多系统疾病。在 46%的 T-PLL 病例中报告了 ATM 序列突变，但有些病例在 11q 也有核型异常，包括 11q23。这促使我们对一组 8 例病例的 ATM 基因座结构进行研究，其中 2 例有 11q23 异常。正如预期的那样，在一些样本中检测到了核苷酸变化。两个缓解期样本为野生型。为了检测结构损伤，将 DNA 纤维与跨越 ATM 基因座的四个标记黏粒的重叠群进行杂交。在所有样本中都存在结构损伤，并且在四个样本中两个等位基因都受到影响。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观点提供了有力证据。由于除了破坏两个等位基因的结构损伤外还存在核苷酸变化，ATM 在 T-PLL 肿瘤发生过程中可能还有其他作用。失活机制似乎不寻常，因为经常在一个等位基因上观察到多个结构损伤。
