继发性和治疗相关急性髓性白血病的分子和基因组景观。

American journal of blood research Pub Date : 2021-10-15 eCollection Date: 2021-01-01
Harsh Goel, Ekta Rahul, Ishan Gupta, Anita Chopra, Amar Ranjan, Aditya Kumar Gupta, Jagdish Prasad Meena, Ganesh Kumar Viswanathan, Sameer Bakhshi, Aroonima Misra, Showket Hussain, Ritesh Kumar, Archana Singh, G K Rath, Ashok Sharma, Sandeep Mittan, Pranay Tanwar
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引用次数: 0

摘要

急性髓系白血病(AML)是一种复杂的侵袭性髓系肿瘤,其特征是频繁的体细胞突变影响不同功能类别的基因,导致成熟停滞和克隆扩增。AML可以从头开始(dn-AML),也可以是继发性AML (s-AML),指的是可能由先前的血液学疾病(AHD-AML)引起的白血病过程,主要来自骨髓增生异常综合征(MDS)或骨髓增生性肿瘤(MPN),也可以是先前的细胞毒性化疗或放射治疗的结果(治疗相关AML, t-AML)。继发性和治疗相关AML的临床和生物学特征与新发AML不同。继发性和治疗相关的AML主要发生在老年人群中,由于对细胞毒性化疗的耐药性,治疗反应较差,复发率较高。在过去的十年中,分子遗传学的进展揭示了继发性和治疗相关AML的亚克隆结构。最近的研究表明,细胞遗传学异常和潜在的遗传畸变(突变)可能是决定预后和对治疗结果产生关键影响的重要因素。与新发AML相比,继发性和治疗相关的AML预后较差,有不良的细胞遗传学异常和较高的不良突变复发率。在这篇综述中,我们概述了继发性和治疗相关AML的临床特征,并讨论了与继发性白血病发病机制有关的基因突变的功能。详细的发病机制知识概述了新的预后标志物,包括可靶向突变,这可能会导致设计和开发针对继发性和治疗相关AML的新型分子靶向治疗。尽管在了解继发性和治疗相关AML的遗传方面取得了重大进展,但其对疾病病理生理的影响,标准治疗前景在过去三十年中没有显着发展。因此,我们总结了继发性和治疗相关的急性髓系白血病的现代和发展的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Molecular and genomic landscapes in secondary & therapy related acute myeloid leukemia.

Molecular and genomic landscapes in secondary & therapy related acute myeloid leukemia.

Acute myeloid leukemia (AML) is a complex, aggressive myeloid neoplasm characterized by frequent somatic mutations that influence different functional categories' genes, resulting in maturational arrest and clonal expansion. AML can arise de novo (dn-AML) or can be secondary AML (s-AML) refers to a leukemic process which may arise from an antecedent hematologic disorder (AHD-AML), mostly from a myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or can be the result of an antecedent cytotoxic chemotherapy or radiation therapy (therapy-related AML, t-AML). Clinical and biological features in secondary and therapy-related AML are distinct from de novo AML. Secondary and therapy-related AML occurs mainly in the elderly population and responds worse to therapy with higher relapse rates due to resistance to cytotoxic chemotherapy. Over the last decade, advances in molecular genetics have disclosed the sub-clonal architecture of secondary and therapy-related AML. Recent investigations have revealed that cytogenetic abnormalities and underlying genetic aberrations (mutations) are likely to be significant factors dictating prognosis and critical impacts on treatment outcome. Secondary and therapy-related AML have a poorer outcome with adverse cytogenetic abnormalities and higher recurrences of unfavorable mutations compared to de novo AML. In this review, we present an overview of the clinical features of secondary and therapy-related AML and address the function of genetic mutations implicated in the pathogenesis of secondary leukemia. Detailed knowledge of the pathogenetic mechanisms gives an overview of new prognostic markers, including targetable mutations that will presumably lead to the designing and developing novel molecular targeted therapies for secondary and therapy-related AML. Despite significant advances in knowing the genetic aspect of secondary and therapy-related AML, its influence on the disease's pathophysiology, standard treatment prospects have not significantly evolved during the past three decades. Thus, we conclude this review by summarizing the modern and developing treatment strategies in secondary and therapy-related acute myeloid leukemia.

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American journal of blood research
American journal of blood research MEDICINE, RESEARCH & EXPERIMENTAL-
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