Aplastic anemia and clonal evolution: germ line and somatic genetics.
Aplastic anemia and clonal evolution: germ line and somatic genetics.
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DOI：
10.1182/asheducation-2016.1.74
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发表时间：
2016-12-02
期刊：
影响因子：
--
通讯作者：
Shimamura A
中科院分区：
文献类型：
--
作者：
Shimamura A
骨髓增生异常综合征（MDS）或急性髓性白血病（AML）的克隆进展仍然是一个可怕的并发症的一个子集的患者骨髓衰竭（BMF）。认识到MDS或AML发展的风险因素将为个性化治疗决策提供信息，并确定可能从早期或前期造血干细胞移植中受益的患者。现在，下一代DNA测序可在临床实验室中使用，研究重点是生殖系和体细胞突变对诊断和监测BMF患者的影响。大多数生殖系遗传BMF病症的特征在于发展MDS或AML的高倾向性。许多受影响的患者缺乏传统上与遗传性骨髓衰竭综合征相关的身体上的污点。尽管任何单一的遗传性骨髓衰竭疾病都是罕见的，但允许同时评估骨髓衰竭基因的多重基因测序表明，作为一个群体，这些遗传性疾病构成了BMF患者的重要子集（5%至10%）。生殖系遗传性骨髓衰竭疾病的早期诊断允许个体化监测和定制治疗。骨髓衰竭的体细胞变异的最新研究揭示了高频率的克隆造血与MDS或AML相关基因突变的收购。对骨髓衰竭中的体细胞突变的研究揭示了促进克隆性疾病机制的重要见解，但也提出了其他问题。这篇综述将集中在生殖细胞和体细胞突变的发展与BMF患者的克隆性疾病的评估和影响。将探讨临床基因检测的挑战和局限性。
Clonal progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) remains a dreaded complication for a subset of patients with bone marrow failure (BMF). Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germ line and somatic mutations for diagnosing and monitoring patients with BMF. Most germ line genetic BMF disorders are characterized by a high propensity to develop MDS or AML. Many affected patients lack the physical stigmata traditionally associated with the inherited marrow failure syndromes. Although any single inherited marrow failure disorder is rare, multiplexed genetic sequencing that allows simultaneous evaluation of marrow failure genes en masse demonstrated that, as a group, these inherited disorders compose a significant subset (5% to 10%) of patients with BMF. Early diagnosis of a germ line genetic marrow failure disorder allows individualized monitoring and tailored therapy. Recent studies of somatic variants in marrow failure revealed a high frequency of clonal hematopoiesis with the acquisition of mutations in genes associated with MDS or AML. Investigation of somatic mutations in marrow failure revealed important insights into the mechanisms promoting clonal disease but also raised additional questions. This review will focus on the evaluation and implications of germ line and somatic mutations for the development of clonal disorders in patients with BMF. Challenges and limitations of clinical genetic testing will be explored.
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影响因子：
11.4
作者：
通讯作者：
--
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
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作者：
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通讯作者：
McCarroll SA
影响因子：
5.7
作者：
Ballmaier, Matthias;Germeshausen, Manuela
通讯作者：
Germeshausen, Manuela
影响因子：
1.9
作者：
Babushok DV;Perdigones N;Perin JC;Olson TS;Ye W;Roth JJ;Lind C;Cattier C;Li Y;Hartung H;Paessler ME;Frank DM;Xie HM;Cross S;Cockroft JD;Podsakoff GM;Monos D;Biegel JA;Mason PJ;Bessler M
通讯作者：
Bessler M
DOI：
10.3324/haematol.2011.055269
发表时间：
2012-03-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Alter, Blanche P.;Rosenberg, Philip S.;Savage, Sharon A.
通讯作者：
Savage, Sharon A.