32个唐氏综合征家庭的细胞遗传学和分子研究：21号染色体长臂最近端区段在白血病易感性中的潜在作用

Cytogenetic and molecular study of 32 Down syndrome families: potential leukaemia predisposing role of the most proximal segment of chromosome 21q.

作者信息

Cavani S, Perfumo C, Argusti A, Pierluigi M, Perroni L, Schmiegelow K, Petersen M B, Cotter F E, Strigini P, Dagna-Bricarelli F, Nizetić D

机构信息

Human Genetics Laboratory, Galliera Hospital, Genoa, Italy.

出版信息

Br J Haematol. 1998 Oct;103(1):213-6. doi: 10.1046/j.1365-2141.1998.00924.x.

DOI:10.1046/j.1365-2141.1998.00924.x

PMID:9792310

Abstract

Down syndrome (DS) children have a 10-20-fold increased risk of developing ALL or AML compared to non-DS children. An increased disomic homozygosity of the polymorphic DNA markers in the pericentromeric region of chromosome 21q (21q11) has repeatedly been found in DS patients with ANLL-M7 and DS-specific transient abnormal myelopoiesis (TAM), compared to the majority of DS subjects without leukaemia. Analysis of cytogenetic heteromorphisms and 26 polymorphic DNA markers from chromosome 21q showed an increased number of pericentromeric crossovers between the non-disjoined chromosomes in DS-ANLL cases (3/11), compared to DS-ALL (0/9) and DS-nonleukaemic cases (0/12). These findings are compatible with the model of disomic homozygosity of the predisposing allele of a putative pericentromeric gene, as an explanation for the high prevalence of ANLL in DS.

摘要

与非唐氏综合征（DS）儿童相比，DS儿童患急性淋巴细胞白血病（ALL）或急性髓系白血病（AML）的风险增加了10至20倍。与大多数无白血病的DS患者相比，在患有急性非淋巴细胞白血病M7型（ANLL-M7）和DS特异性短暂异常髓系造血（TAM）的DS患者中，反复发现21号染色体长臂（21q）着丝粒周围区域的多态性DNA标记的二体纯合性增加。对细胞遗传学异态性和21号染色体长臂的26个多态性DNA标记的分析表明，与DS-ALL（0/9）和DS非白血病病例（0/12）相比，DS-ANLL病例（3/11）中未分离染色体之间的着丝粒周围交叉数量增加。这些发现与假定的着丝粒周围基因的易感等位基因二体纯合性模型相符，以此作为DS中ANLL高患病率的一种解释。