The route to development of myelodysplastic syndrome/acute myeloid leukaemia in Shwachman-Diamond syndrome: the role of ageing, karyotype instability, and acquired chromosome anomalies
The route to development of myelodysplastic syndrome/acute myeloid leukaemia in Shwachman-Diamond syndrome: the role of ageing, karyotype instability, and acquired chromosome anomalies
复制标题
DOI：
10.1111/j.1365-2141.2009.07611.x
复制
发表时间：
2009-04-01
影响因子：
6.5
通讯作者：
Pasquali, Francesco
中科院分区：
文献类型：
--
作者：
Maserati, Emanuela;Pressato, Barbara;Pasquali, Francesco
对22例新的Shwachman-Diamond综合征（SDS）患者的调查和对14例先前报道的病例的随访显示：（i）36例病例中有16例骨髓（BM）中存在7号和20号染色体的克隆性染色体变化，但如果考虑非克隆性变化，影响这些染色体的异常频率为20/36：（ii）复发性等染色体i（7）（q10）不包括短臂物质，而它保留了两个D 7Z 1 α序列阵列;（iii）缺失del（20）（q11）涉及骨髓增生异常综合征（MDS）和急性髓性白血病（AML）典型的最小缺失区域;（iv）在具有在短臂上携带额外物质的染色体7的BM克隆的快速扩增期间，仅一名患者发展MDS;（v）BM克隆染色体异常的获得与年龄相关。我们的结论是，核型不稳定性是SDS的自然史的一部分，通过一个特定的突变效应，与缺乏SBDS蛋白，随之而来的克隆异常的7号和20号染色体在骨髓中，这可能最终促进MDS/AML与患者的老龄化。
An investigation of 22 new patients with Shwachman-Diamond syndrome (SDS) and the follow-up of 14 previously reported cases showed that (i) clonal chromosome changes of chromosomes 7 and 20 were present in the bone marrow (BM) of 16 out of 36 cases, but if non-clonal changes were taken into account, the frequency of anomalies affecting these chromosomes was 20/36: a specific SDS karyotype instability was thus confirmed; (ii) the recurrent isochromosome i(7)(q10) did not include short arm material, whereas it retained two arrays of D7Z1 alphoid sequences; (iii) the deletion del(20)(q11) involved the minimal region of deletion typical of myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML); (iv) only one patient developed MDS, during the rapid expansion of a BM clone with a chromosome 7 carrying additional material on the short arms; (v) the acquisition of BM clonal chromosome anomalies was age-related. We conclude that karyotype instability is part of the natural history of SDS through a specific mutator effect, linked to lacking SBDS protein, with consequent clonal anomalies of chromosomes 7 and 20 in BM, which may eventually promote MDS/AML with the patients' ageing.