Blood Cancer and Stem Cells, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, NG7 2RD, UK.
Sci Rep. 2020 Oct 19;10(1):17695. doi: 10.1038/s41598-020-73782-x.
Nucleophosmin is commonly both over-expressed and mutated in acute myeloid leukemia (AML). NPM1 mutations are always heterozygous. In addition, NPM1 has a number of different splice variants with the major variant encoded by exons 1-9 and 11-12 (NPM1.1). Further variants include NPM1.2 which lacks exons 8 and 10 and NPM1.3 which comprises exons 1-10 (and so lacks the region of sequence mutated in AML). In this study we quantified the expression of these three variants in 108 AML patient samples with and without NPM1 mutations and also assessed the level of expression from the wild-type and mutant alleles in variants NPM1.1 and NPM1.2. The results show that NPM1.1 is the most commonly expressed variant, however transcripts from wild-type and mutated alleles do not occur at equal levels, with a significant bias toward the mutated allele. Considering the involvement of mutant nucleophosmin in the progression and maintenance of AML, a bias towards mutated transcripts could have a significant impact on disease maintenance.
核仁磷酸蛋白在急性髓系白血病（AML）中通常既过度表达又发生突变。NPM1 突变总是杂合的。此外，NPM1 有许多不同的剪接变体，主要变体由外显子 1-9 和 11-12 编码（NPM1.1）。进一步的变体包括缺乏外显子 8 和 10 的 NPM1.2 和包含外显子 1-10 的 NPM1.3（因此缺乏 AML 中突变的序列区域）。在这项研究中，我们定量分析了 108 例有和没有 NPM1 突变的 AML 患者样本中这三种变体的表达情况，还评估了 NPM1.1 和 NPM1.2 变体中野生型和突变型等位基因的表达水平。结果表明，NPM1.1 是最常表达的变体，然而野生型和突变型等位基因的转录本并不以相等的水平存在，而是偏向于突变型等位基因。考虑到突变核仁磷酸蛋白在 AML 的进展和维持中的参与，偏向于突变型转录本可能对疾病的维持产生重大影响。
