Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2αB gene associated with myeloblastic leukemias
Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2αB gene associated with myeloblastic leukemias
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DOI：
10.1182/blood.v93.6.1817.406k36_1817_1824
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发表时间：
1999-03-15
期刊：
影响因子：
20.3
通讯作者：
Ito, Y
中科院分区：
文献类型：
--
作者：
Osato, M;Asou, N;Ito, Y
编码异二聚体转录因子Runt结构域家族中DNA结合α亚基的AML 1基因因其频繁参与与白血病相关的染色体易位而被注意到。采用逆转录聚合酶链反应（RT-PCR）结合非同位素核糖核酸酶裂解试验（NIRCA）检测160例白血病患者中8例AML 1基因点突变：沉默突变2例，杂合错义突变4例，双等位基因无义或移码突变2例。突变全部聚集在punt结构域内。在3例患者中发现的错义突变既不显示DNA结合也不显示反式激活，尽管在异源二聚体中是活跃的。这些有缺陷的错义突变体可能与白血病的易感性或进展有关。另一方面，编码截短的AML 1蛋白的双等位基因无义突变体几乎失去了所有检查的功能，并可能在导致急性髓细胞白血病的白血病发生中发挥作用。(C)1999年，美国血液学会。
The AML1 gene encoding the DNA-binding alpha-subunit in the Runt domain family of heterodimeric transcription factors has been noted for its frequent involvement in chromosomal translocations associated with leukemia. Using reverse transcriptase-polymerase chain reaction (RT-PCR) combined with nonisotopic RNase cleavage assay (NIRCA), we found point mutations of the AML1 gene in 8 of 160 leukemia patients: silent mutations, heterozygous missense mutations, and biallelic nonsense or frameshift mutations in 2, 4, and 2 cases, respectively. The mutations were all clustered within the punt domain. Missense mutations identified in 3 patients showed neither DNA binding nor transactivation, although being active in heterodimerization. These defective missense mutants may be relevant to the predisposition or progression of leukemia. On the other hand, the biallelic nonsense mutants encoding truncated AML1 proteins lost almost all functions examined and may play a role in leukemogenesis leading to acute myeloblastic leukemia. (C) 1999 by The American Society of Hematology.