Molecular lesions in childhood and adult acute megakaryoblastic leukaemia
Molecular lesions in childhood and adult acute megakaryoblastic leukaemia
复制标题
DOI：
10.1111/j.1365-2141.2011.08948.x
复制
发表时间：
2012-02-01
影响因子：
6.5
通讯作者：
Maciejewski, Jaroslaw P.
中科院分区：
文献类型：
--
作者：
Hama, Asahito;Muramatsu, Hideki;Maciejewski, Jaroslaw P.
虽然急性巨核细胞白血病 (AMKL) 发生在患有唐氏综合症 (DS-AMKL) 和不患有唐氏综合症（儿童非 DS-AMKL）的儿童中，但它也可能影响不患有唐氏综合症的成人（成人非 DS-AMKL）。我们分析了这些患者亚组（11 名 DS-AMKL 儿童、12 名儿童和 4 名非 DS-AMKL 成人）是否存在分子病变，包括分别通过测序和基于单核苷酸多态性阵列的核型分析研究的突变和染色体异常。在儿童中，AMKL 与 21 三体性（非 DS-AMKL 中的体细胞）相关，而 21 号染色体的数值畸变很少与成人 AMKL 相关。 DS-AMKL 还与 1q 复发性体细胞增益相关（4/11 DS-AMKL 患者）。与 21 三体性和 1q 增益相反，其他额外的染色体病变在 AMKL 儿童和成人之间均匀分布。突变筛查发现 11/12 DS-AMKL 中存在 GATA1 突变，但在儿童非 DS-AMKL (1/12) 和成人 AMKL (0/4) 中突变很少见。 JAK3 (1/11)、JAK2 (1/11) 和 TP53 突变 (1/11) 仅在 DS-AMKL 患者中发现。在所有研究的患者组中均未发现 ASXL1、IDH1/2、DNMT3A、RUNX1 和 CBL 突变，而在两名儿童非 DS-AMKL 患者中发现了 NRAS 突变。
While acute megakaryoblastic leukaemia (AMKL) occurs in children with (DS-AMKL) and without (paediatric non-DS-AMKL) Down syndrome, it can also affect adults without DS (adult non-DS-AMKL). We have analysed these subgroups of patients (11 children with DS-AMKL, 12 children and four adults with non-DS-AMKL) for the presence of molecular lesions, including mutations and chromosomal abnormalities studied by sequencing and single nucleotide polymorphism array-based karyotyping, respectively. In children, AMKL was associated with trisomy 21 (somatic in non-DS-AMKL), while numerical aberrations of chromosome 21 were only rarely associated with adult AMKL. DS-AMKL was also associated with recurrent somatic gains of 1q (4/11 DS-AMKL patients). In contrast to trisomy 21 and gains of 1q, other additional chromosomal lesions were evenly distributed between children and adults with AMKL. A mutational screen found GATA1 mutations in 11/12 DS-AMKL, but mutations were rare in paediatric non-DS-AMKL (1/12) and adult AMKL (0/4). JAK3 (1/11), JAK2 (1/11), and TP53 mutations (1/11) were found only in patients with DS-AMKL. ASXL1, IDH1/2, DNMT3A, RUNX1 and CBL mutations were not found in any of the patient group studied, while NRAS mutation was identified in two patients with paediatric non-DS-AMKL.