Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms
Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms
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DOI：
10.1182/blood-2012-09-399725
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发表时间：
2013-01-10
期刊：
影响因子：
20.3
通讯作者：
Malcovati, Luca
中科院分区：
文献类型：
--
作者：
Cazzola, Mario;Rossi, Marianna;Malcovati, Luca
前体mRNA剪接由剪接体催化，剪接体是由与蛋白质相关的小核RNA组成的大分子。SF 3B 1基因编码剪接因子3b的亚基1，其对于将剪接体锚定到前体mRNA是重要的。2011年，全外显子组测序研究显示，在骨髓增生异常综合征或骨髓增生异常/骨髓增生性肿瘤患者中，SF 3B 1和RNA剪接机制的其他基因发生了复发性体细胞突变。SF 3B 1突变在以环形铁粒幼细胞为特征的疾病中频率特别高，这与因果关系一致。SF 3B 1突变体在多种其他肿瘤类型中也以较低的频率检测到。在慢性淋巴细胞白血病中，SF 3B 1被发现是第二个最常见的突变基因。在骨髓增生异常综合征中，SF 3B 1突变似乎是遗传性病变的基础，并与白血病进展的低风险相关。相比之下，SF 3B 1突变在慢性淋巴细胞白血病早期的发生率较低，在晚期疾病中更常见，并且往往与预后不良相关，这表明它们发生在疾病的克隆进化过程中。SF 3B 1突变状态的评估可能成为创新的诊断和预后工具，剪接体调节剂的可用性开辟了新的治疗前景。（血。2013;121（2）：260-269）
Precursor mRNA splicing is catalyzed by the spliceosome, a macromolecule composed of small nuclear RNAs associated with proteins. The SF3B1 gene encodes subunit 1 of the splicing factor 3b, which is important for anchoring the spliceosome to precursor mRNA. In 2011, whole-exome sequencing studies showed recurrent somatic mutations of SF3B1 and other genes of the RNA splicing machinery in patients with myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm. SF3B1 mutations had a particularly high frequency among conditions characterized by ring sideroblasts, which is consistent with a causal relationship. SF3B1 mutants were also detected at a lower frequency in a variety of other tumor types. In chronic lymphocytic leukemia, SF3B1 was found to be the second most frequently mutated gene. In myelodysplastic syndromes, SF3B1 mutations appear to be founding genetic lesions and are associated with a low risk of leukemic evolution. In contrast, SF3B1 mutations have a lower incidence in early stages of chronic lymphocytic leukemia, are more common in advanced disease, and tend to be associated with poor prognosis, suggesting that they occur during clonal evolution of the disease. The assessment of SF3B1 mutation status may become innovative diagnostic and prognostic tools and the availability of spliceosome modulators opens novel therapeutic prospects. (Blood. 2013;121(2):260-269)