Monitoring treatment response and disease progression in myeloma with circulating cell‐free DNA
| العنوان: | Monitoring treatment response and disease progression in myeloma with circulating cell‐free DNA |
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| المؤلفون: | Sharmilan Thanendrarajan, Shayu Deshpande, Frits van Rhee, Gareth J. Morgan, Ruslana Tytarenko, Faith E. Davies, Carolina Schinke, Brian A Walker, Eileen M Boyle, Yan Wang, Cody Ashby, Fenghuang Zhan, Maurizio Zangari |
| المصدر: | European Journal of Haematology. 106:230-240 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Smoldering Multiple Myeloma, Oncology, medicine.medical_specialty, medicine.medical_treatment, medicine.disease_cause, Circulating Tumor DNA, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Bone Marrow, Lactate dehydrogenase, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Humans, Medicine, Alleles, Multiple myeloma, Chemotherapy, business.industry, Beta-2 microglobulin, Hazard ratio, Liquid Biopsy, Computational Biology, Genetic Variation, High-Throughput Nucleotide Sequencing, Hematology, General Medicine, Prognosis, medicine.disease, Circulating Cell-Free DNA, Tumor Burden, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Concomitant, Disease Progression, ras Proteins, KRAS, Multiple Myeloma, business, 030215 immunology |
| الوصف: | Circulating cell-free DNA (cfDNA) has the potential to capture spatial genetic heterogeneity in myeloma (MM) patients. We assessed whether cfDNA levels vary according to risk status defined by the 70 gene expression profile (GEP70). cfDNA levels in 77 patients were significantly higher in the GEP70 high-risk (HR) group compared to the low-risk (LR) group and correlated weakly with clinical markers including lactate dehydrogenase, β2 -microglobulin, and ISS. Patients with high cfDNA levels were associated with a worse PFS (hazard ratio 6.4; 95% CI of ratio 1.9-22) and OS (hazard ratio 4.4; 95% CI of ratio 1.2-15.7). Circulating tumor DNA (ctDNA) was elevated in the HR group and ctDNA correlated strongly with GEP70 risk score (Spearman r = .69, P = .0027). cfDNA concentrations were significantly elevated between days 3-5 after chemotherapy before falling back to baseline levels. ctDNA in two patients showed a similar spike in levels between days 3 and 5 after chemotherapy with a concomitant increase in allele fraction of KRAS mutations. We assessed cfDNA levels in 25 patients with smoldering myeloma with serial samples and showed increased allele fraction of mutated KRAS at progression in cfDNA. Our study shows that cfDNA is a dynamic tool to capture genetic events in myeloma. |
| تدمد: | 1600-0609 0902-4441 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a011598ae66c6e382f7e114dacf1411Test https://doi.org/10.1111/ejh.13541Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....9a011598ae66c6e382f7e114dacf1411 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16000609 09024441 |
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