Targeted, Amplicon-Based, Next-Generation Sequencing to Detect Age-Related Clonal Hematopoiesis

Snetsinger, Brooke; Ferrone, Christina K.; Rauh, Michael J.

doi:10.1007/7651_2019_216

Cited by 12 publications

(10 citation statements)

References 20 publications

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“…1. Age: Older adults > 60 years of age [2,27,89] 2. Blood status: Patients with unexplained anemia or aberrant laboratory parameters (altered myeloid cell/erythroid cell ratio or myeloid/lymphoid ratio) may be associated with an underlying stem cell disorder [90,91] 3.…”

Section: Patient Screeningmentioning

confidence: 99%

Personalized Cell Therapy for Patients With Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-based Responder and Non-responder Prediction

Salybekov¹,

Wolfien²,

Kobayashi³

et al. 2021

Preprint

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Stem/progenitor cell transplantation is a potential novel therapeutic strategy to induce angiogenesis in ischemic tissue, which can prevent major amputation in patients with advanced peripheral artery disease (PAD). Thus, clinicians can use cell therapies worldwide to treat PAD. However, some cell therapy studies did not report beneficial outcomes. Clinical researchers suggested that classical risk factors and comorbidities may adversely affect the efficacy of cell therapy. Some studies have indicated that the response to stem cell therapy varies among patients even in those harboring limited risk factors. This suggested the role of undetermined risk factors, including genetic alterations, somatic mutations, and clonal hematopoiesis. Personalized stem cell-based therapy can be developed by analyzing individual risk factors. These approaches must consider several clinical biomarkers and perform studies (such as genome-wide association studies (GWAS)) on disease-related genetic traits and integrate the findings with those of transcriptome-wide association studies (TWAS) and whole-genome sequencing in PAD. Additional unbiased analyses with state-of-the-art computational methods, such as machine learning-based patient stratification, are suited for predictions in clinical investigations. The integration of these complex approaches into a unified analysis procedure for the identification of responders and non-responders before stem cell therapy, which can decrease treatment expenditure, is a major challenge to increase the efficacy of therapies.

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Section: Patient Screeningmentioning

confidence: 99%

Personalized Cell Therapy for Patients With Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-based Responder and Non-responder Prediction

Salybekov¹,

Wolfien²,

Kobayashi³

et al. 2021

Preprint

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“…Regarding NGS, there is currently no consensus on the exact genetic target regions (or even numbers of genes) to be assessed to detect CHIP. The approaches range from very small panels focusing only on mutational hotspots [ 47 ], to small panels including the most frequently mutated genes in CHIP [ 43 , 48 ] or standard panels for myeloid neoplasms [ 29 ], to WES [ 1 , 2 , 8 ] or whole genome sequencing (WGS) [ 49 ]. Likewise, the analysis of WES/WGS data have either been limited to mutations in putative driver genes (e.g., the assessment of variants in 74 genes known to be recurrently mutated in myeloid cancers [ 8 ]) or included all somatic variants irrespective of their driver status [ 1 , 49 ].…”

Section: Detection Of Clonal Hematopoiesismentioning

confidence: 99%

Clonal Hematopoiesis of Indeterminate Potential: A Multidisciplinary Challenge in Personalized Hematology

Hoermann

Greiner

Griesmacher

et al. 2020

JPM

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Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related condition that represents a potential pre-phase of hematologic neoplasm. Next-generation sequencing (NGS) is used to detect and monitor clonal hematopoiesis, and the spectrum of mutations substantially overlaps with that of myeloid neoplasms with DNMT3A, TET2, ASXL1, and JAK2 being the most frequently mutated. While, in general, the risk of progression to an overt myeloid neoplasm is only modest, the progression risk increases in patients with unexplained cytopenia or multiple mutations. In addition, CHIP represents a previously unrecognized major risk factor for atherosclerosis and cardiovascular disease (CVD), including coronary heart disease, degenerative aortic valve stenosis, and chronic heart failure; and a causative role of CHIP in the development of CVD has been demonstrated in vitro and in vivo. The management of patients with CHIP is a rapidly emerging topic in personalized medicine, as NGS has become widely available for clinical medicine. It requires a highly multidisciplinary setting, including hematology/oncology, cardiology, (clinical) pathology, and genetics for individualized guidance. Further research is urgently needed to provide robust evidence for future guidelines and recommendations on the management of patients with CHIP in the era of personalized medicine.

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“…The detection of mutations in this gene could, therefore, be a component of a group of tests to predict a higher risk of myeloid malignancies [138,139]. Techniques used to detect DNMT3A mutations include DNA sequencing, high-resolution DNA melting, restriction fragment length polymorphism, and denaturing high-performance liquid chromatography [140,141,142,143,144]. A microsphere-based suspension assay that utilizes oligonucleotide analogs, LNA- or BNA NC -containing, as probes specific for wild type or mutant alleles was more efficient than direct sequencing [96].…”

Section: Bnancmentioning

confidence: 99%

Bridged Nucleic Acids Reloaded

2019

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Oligonucleotides are key compounds widely used for research, diagnostics, and therapeutics. The rapid increase in oligonucleotide-based applications, together with the progress in nucleic acids research, has led to the design of nucleotide analogs that, when part of these oligomers, enhance their efficiency, bioavailability, or stability. One of the most useful nucleotide analogs is the first-generation bridged nucleic acids (BNA), also known as locked nucleic acids (LNA), which were used in combination with ribonucleotides, deoxyribonucleotides, or other analogs to construct oligomers with diverse applications. However, there is still room to improve their efficiency, bioavailability, stability, and, importantly, toxicity. A second-generation BNA, BNANC (2′-O,4′-aminoethylene bridged nucleic acid), has been recently made available. Oligomers containing these analogs not only showed less toxicity when compared to LNA-containing compounds but, in some cases, also exhibited higher specificity. Although there are still few applications where BNANC-containing compounds have been researched, the promising results warrant more effort in incorporating these analogs for other applications. Furthermore, newer BNA compounds will be introduced in the near future, offering great hope to oligonucleotide-based fields of research and applications.

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Targeted, Amplicon-Based, Next-Generation Sequencing to Detect Age-Related Clonal Hematopoiesis

Cited by 12 publications

References 20 publications

Personalized Cell Therapy for Patients With Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-based Responder and Non-responder Prediction

Personalized Cell Therapy for Patients With Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-based Responder and Non-responder Prediction

Clonal Hematopoiesis of Indeterminate Potential: A Multidisciplinary Challenge in Personalized Hematology

Bridged Nucleic Acids Reloaded

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