近日,，研究人員發(fā)現(xiàn)BAALC基因在急性白血病細胞過度激活,，這一發(fā)現(xiàn)可能白血病治療提供一個預(yù)后指標(biāo),。
這項研究發(fā)現(xiàn)BAALC過度表達是由單核苷酸多態(tài)性引發(fā)的,，單核苷酸多態(tài)性開啟基因的的表達,，當(dāng)基因關(guān)閉時,，單核苷酸多態(tài)性允許不同的分子保持該基因的運行,。
分子生物學(xué)和癌癥遺傳學(xué)專家、首席研究員Albert de la Chapelle博士說：我們想強調(diào)的是單核苷酸多態(tài)性并不提高我們患白血病的風(fēng)險,，但它易引發(fā)BAALC基因的過度表達,，后者與白血病的發(fā)展和治療反應(yīng)不佳有關(guān)。
具體來說，單核苷酸多態(tài)性引起的DNA變化最終活化RUNX1分子,，研究人員發(fā)現(xiàn)RUNX1蛋白水平高的患者BAALC基因表達水平高,，而RUNX1低表達的患者BAALC基因表達也低。
研究論文發(fā)表在PNAS雜志上,，證實了單核苷酸多態(tài)性可能是一個有用的預(yù)后指標(biāo),，能用來指導(dǎo)急性白血病患者的治療。（生物谷：Bioon.com）
doi:10.1073/pnas.1203756109
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Heritable polymorphism predisposes to high BAALC expression in acute myeloid leukemia
Ann-Kathrin Eisfelda, Guido Marcuccia, Sandya Liyanarachchia, Konstanze D?hnerb, Sebastian Schwinda, Kati Maharrya,c, et al.
Overexpression of the brain and acute leukemia, cytoplasmic (BAALC) gene is implicated in myeloid leukemogenesis and associated with poor outcome in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia patients. Additionally, high BAALC expression occurs in glioblastoma, melanoma, and childhood gastrointestinal stroma tumors, suggesting an oncogenic role for BAALC. However, the mechanisms underlying the deregulated expression are unknown. We hypothesized that a common heritable genetic feature located in cis might account for overexpression of BAALC in an allele-specific manner. By sequencing the genomic region of BAALC we identified nine informative single nucleotide polymorphisms (SNPs) and tested them for a possible association with BAALC expression levels. We show that BAALC overexpression occurs in the presence of the T allele of SNP rs62527607[GT], which creates a binding site for the activating RUNX1 transcription factor in the BAALC promoter region. The mechanism is demonstrated experimentally in vitro using luciferase reporter assays and electrophoretic mobility shift assay (EMSA) analysis. The association of high BAALC expression with the T allele and its correlations with RUNX1 expresser status are shown in vivo in a test set (n = 253) and validation set (n = 105) of samples from cytogenetically normal AML patients from different populations. Thus, we identify a heritable genomic feature predisposing to overexpression of an oncogene, thereby possibly leading to enhanced AML leukemogenesis. Our findings further suggest that genomic variants might become useful tools in the practice of personalized medicine.
