Next-Generation Sequencing Analysis in Posttransplant Relapsed Acute Myeloid Leukemia Reveals Clonal Evolution and Donor-Derived Germline Variant Indicating Bone Marrow Chimerism

IF 0.2
M. Kroloff, G. Crane, R. Press, Stephen Lee, Sarah M. Larson, Rena R. Xian
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Abstract

The era of next-generation sequencing (NGS) has led to a deeper understanding of the genetic complexity and heterogeneity of this disease, in addition to revealing mechanisms of disease relapse. Clinical NGS is becoming routine in clinical practice in both solid organ and hematologic malignancies to identify molecular markers of disease that might assist with diagnosis, prognosis, and the treatment of cancer. These tumor-specific markers also enable treatment response monitoring, as they serve as clonal markers unique to the disease. Continuous molecular monitoring also allows identification of disease recurrence with potentially new actionable mutations. This practice is complicated in the setting of allogeneic bone marrow transplant, as the admixtures of donor and recipient DNA pose unique challenges to NGS interpretation. This case highlights the importance of systematic methodological interpretation of NGS results to better understand the clinical significance and impact of new mutations discovered posttransplant and reveals another potential application of NGS for bone marrow engraftment analysis.
移植后复发急性髓系白血病的新一代测序分析揭示了克隆进化和供体来源的种系变异表明骨髓嵌合
下一代测序(NGS)时代的到来使得人们对这种疾病的遗传复杂性和异质性有了更深入的了解,同时也揭示了疾病复发的机制。临床NGS正在成为实体器官和血液恶性肿瘤的常规临床实践,以确定可能有助于癌症诊断、预后和治疗的疾病分子标志物。这些肿瘤特异性标记物也能够监测治疗反应,因为它们是该疾病特有的克隆标记物。连续的分子监测也允许识别疾病复发与潜在的新的可操作的突变。这种做法在同种异体骨髓移植的情况下是复杂的,因为供体和受体DNA的混合物给NGS解释带来了独特的挑战。该病例强调了对NGS结果进行系统方法学解释的重要性,以更好地了解移植后发现的新突变的临床意义和影响,并揭示了NGS在骨髓移植分析中的另一种潜在应用。
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期刊介绍: Each issue of Pathology Case Reviews examines one vital theme in the field with peer-reviewed, clinically oriented case reports that focus on diagnosis, specimen handling and reports generation. Each theme-oriented issue covers both histopathologic and cytopathologic cases, offering a comprehensive perspective that includes editorials and review articles of the newest developments in the field, differential diagnosis hints, applications of new technologies, reviews of current issues and techniques and an emphasis on new approaches.
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