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首页> 外文期刊>Journal of the advanced practitioner in oncology >Clinical implications of Molecular Analysis for Advanced Practice Providers Caring for Newly Diagnosed Acute Myeloid Leukemia Patients
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Clinical implications of Molecular Analysis for Advanced Practice Providers Caring for Newly Diagnosed Acute Myeloid Leukemia Patients

机译：高级实践提供商的分子分析对新诊断的急性髓性白血病患者的临床意义

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Purpose: Acute myeloid leukemia (AML) patients can have several genetic mutations that allow for risk stratification, prognostication, and yield actionable information that can guide treatment decisions. Our goal is to educate the APP on the importance of genetic mutational analysis in newly diagnosed AML patients and to demonstrate clinical relevance. Methods: The evidence for this abstract was obtained through an extensive literature review (2014-2019) on the topic of gene mutations in AML. Discoveries AML is a heterogeneous myeloid malignancy characterized by acquired genetic alterations of the myeloid progenitor cell His torically, the diagnosis was based on cytogenetic abnormalities alone. Conventional karyotyping reveals - 50% of newly diagnosed AML patients have normal cytogenetics. More recently, techniques such as next generation sequencing (NGS), have confirmed that AML has extensive molecular heterogeneity. These techniques reveal distinct patterns of cooperativity, mutual exclusivity, sub-clonal architecture, and clinical genetic evolution. In AML, 70% of patients with a normal karyotype have at least one gene mutation detected by NGS; with an average of 3 mutations per patient. Both driver and cooperating mutations have been identified by the European Leukemia Net (ELN). These mutations contribute to disease progression/relapse and impact overall survival. Driver mutations are those that present in preleukemic stem cells. Cooperating or subclonal mutations typically develop later in the disease course. Sanger sequencing-based techniques were the first to show that a normal karyotype can still have mutations within key genes (e.g. NPM1, FLT3, CEBPA). There is need for more comprehensive molecular genetic profiling approaches, yet to date there is no consensus on approach or number of genes to evaluate. NGS-based gene panel assays have gained wide clinical acceptance and therefore justifies its use in AML. Genome-wide assays, although more comprehensive than panels, have not been fully validated and remain investigational. Conclusions: In patients with newly diagnosed AML, conventional cytoge-netic analysis is still required per ELN and NCCN guidelines. Gene mutations, both driver and subclonal, both individually and coexisting, can impact clinical outcomes and prognosis. In addition, patients should undergo mutational profiling for at least the following gene mutations: NPM1, CEBPA, RUNX1, FLT3, TP53, ASXL1, BCR-ABL1, IDH1/2. The list of molecular markers will likely continue to increase as single gene testing is replaced with more comprehensive analysis. Having the ability to recognize specific genetic mutations in patients can also enable the diagnosis of AML with blast counts below 20%. Diversity in mutational and chromosomal alterations in AML has led to persistent challenges in defining prognosis. The ELN 2017 risk stratification guidelines integrate both cytogenetic and molecular features to divide patients into three prognostic risk groups (favorable, intermediate, adverse). Implications: The diagnosis of AML relies on technology that incorporates genetic evaluation. As treatment paradigms lean towards a more personalized approach, so must the trends in the care of AML patients. This can allow for risk prognostication and possibly guide treatment decisions. APPs play a vital role in the care of this patient population and must understand the importance of genetic mutational analysis in newly diagnosed AML patients.
机译：目的：急性髓性白血病（AML）患者可以有几种遗传突变，可用于风险分层，预后和产生可以指导治疗决策的可行信息。我们的目标是教育该应用程序对新诊断的AML患者的遗传突变分析的重要性，并证明临床相关性。方法：通过广泛的文献综述（2014-2019）对AML中基因突变议题的大量文献综述（2014-2019）获得了本摘要的证据。发现AML是一种异质骨髓性恶性肿瘤，其特征在于他的症状尿素祖细胞的遗传改变他的扭曲，诊断是基于单独的细胞遗传学异常。常规的核型化揭示 - 50％的新诊断的AML患者具有正常的细胞遗传学。最近，诸如下一代测序（NGS）之类的技术证实AML具有广泛的分子异质性。这些技术揭示了合作，互斥，子克隆架构和临床遗传演进的不同模式。在AML中，70％的正常核型患者具有至少一种由NGS检测到的基因突变;平均每位患者3个突变。欧洲白血病网（eln）鉴定了司机和合作突变。这些突变有助于疾病进展/复发和影响整体存活。司机突变是存在于预期血糖干细胞中的突变。合作或亚间蒙突变通常在疾病过程中发展。基于Sanger测序的技术是第一个显示正常的核型仍然可以在关键基因中具有突变（例如NPM1，FLT3，CEBPA）。需要更全面的分子遗传分析方法，迄今为止没有关于评估的方法或基因数量的共识。基于NGS的基因面板测定临床接受程度广泛，因此证明其在AML中的使用。范围内的测定虽然比面板更全面，但尚未完全验证并保持调查。结论：在新诊断的AML患者中，每个ELN和NCCN指南仍然需要常规的Cytoge-Net-Net-Net。单独和共存的基因突变，司机和亚克隆都可以影响临床结果和预后。此外，患者应至少进行以下基因突变进行突变分析：NPM1，CEBPA，RUNX1，FLT3，TP53，ASXL1，BCR-ABL1，IDH1 / 2。随着单一基因检测更换更全面的分析，分子标记列表可能会继续增加。具有识别患者特异性遗传突变的能力也可以使爆炸计数低于20％的爆炸计数能够诊断AML。 AML中突变和染色体改变的多样性导致定义预后的持续挑战。 ELN 2017风险分层指南将细胞遗传学和分子特征与患者分为三种预后风险群体（有利，中间，不利）。含义：AML的诊断依赖于包含遗传评估的技术。随着治疗范式倾向于更加个性化的方法，因此必须涉及患者的护理趋势。这可以允许风险预测和可能指导治疗决策。 Apps在关注这一患者人口中起着至关重要的作用，并且必须了解遗传突变分析在新诊断的AML患者中的重要性。

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