Leukaemia-related gene expression in bone marrow cells from patients with the preleukaemic disorder Shwachman-Diamond syndrome
Leukaemia-related gene expression in bone marrow cells from patients with the preleukaemic disorder Shwachman-Diamond syndrome
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DOI：
10.1111/j.1365-2141.2007.06608.x
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发表时间：
2007-06-01
影响因子：
6.5
通讯作者：
Dror, Yigal
中科院分区：
文献类型：
--
作者：
Rujkijyanont, Piya;Beyene, Joseph;Dror, Yigal
Shwachman-Diamond综合征（SDS）是一种遗传性骨髓衰竭疾病，伴有血细胞减少症和骨髓增生异常综合征（MDS）和白血病（特别是急性髓性白血病）的高倾向。SDS中白血病发生的机制尚不清楚。根据致癌作用的多次打击理论，在MDS/白血病变得明显之前，可能发生几次分子和细胞打击。本研究使用寡核苷酸芯片，以确定基因表达模式，这被证明是与leukaemogenesis，在骨髓单个核细胞的9个SDS患者没有明显的转化相比，健康对照。在154个已知的白血病相关基因中，发现几个癌基因上调，包括LARG，TAL1和MLL，几个肿瘤抑制基因下调，包括DLEU1，RUNX1，FANCD 2和DKC 1。真实的时间聚合酶链反应证实SDS骨髓中LARG和TAL 1的表达在统计学上更高。我们的结论是SDS骨髓单个核细胞表现出异常的基因表达模式，这可能会导致有利于恶性克隆的演变或进展的持续刺激。其他分子和细胞遗传学事件可能是必要的恶性过程是不可逆的和完整的。
Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure disorder with cytopenia and a high propensity for myelodysplastic syndrome (MDS) and leukaemia, particularly acute myeloid leukaemia. The mechanism of leukaemogenesis in SDS is unknown. In accordance to the multi-hit theory of carcinogenesis, it is likely that several molecular and cellular hits occur before MDS/leukaemia become apparent. This study used oligonucleotide microarray to identify gene expression patterns, which were shown to be associated with leukaemogenesis, in marrow mononuclear cells of nine SDS patients without overt transformation compared to healthy controls. Among 154 known leukaemia-related genes, several oncogenes were found to be upregulated, including LARG, TAL1 and MLL, and of several tumour suppressor genes were downregulated, including DLEU1, RUNX1, FANCD2 and DKC1. Real time polymerase chain reaction confirmed statistically higher expression of LARG and TAL1 in SDS marrows. We conclude that SDS marrow mononuclear cells exhibit abnormal gene expression patterns, which might result in continuous stimulation favouring evolution or progression of malignant clones. Additional molecular and cytogenetic events are probably necessary for the malignant process to be irreversible and complete.