Hiroshi Yasui1, Masayuki Kobayashi2,3, Kota Sato4, Kanya Kondoh2, Tadao Ishida4, Yuta Kaito5, Hideto Tamura5,6, Hiroshi Handa7, Yutaka Tsukune8, Makoto Sasaki8, Norio Komatsu8, Norina Tanaka9, Junji Tanaka9, Masahiro Kizaki10, Toyotaka Kawamata1, Junya Makiyama1, Kazuaki Yokoyama1, Seiya Imoto11, Arinobu Tojo1,2, Yoichi Imai12. 1. Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. 2. Division of Molecular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. 3. Department of Hematology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan. 4. Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan. 5. Department of Hematology, Nippon Medical School, Tokyo, Japan. 6. Division of Diabetes, Endocrinology and Hematology, Department of Internal Medicine, Dokkyo Medical University Saitama Medical Center, Mibu, Japan. 7. Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Japan. 8. Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan. 9. Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan. 10. Department of Hematology, Saitama Medical Center, Saitama Medical University, Saitama, Japan. 11. Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. 12. Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. imaiyo-tky@umin.ac.jp.
Abstract
BACKGROUND: Multiple myeloma (MM) is an incurable hematological malignancy. Despite the introduction of several novel drugs, most patients relapse. Biomarkers to identify the early signs of relapse will make it possible to adjust the therapeutic strategy before the disease worsens. Although understanding genetic changes is important for the treatment of MM, currently known biomarkers of relapse, including serum free-light chains and monoclonal paraproteins, are not associated with genetic changes. METHODS: We therefore performed a multicenter study to examine the usefulness of circulating cell-free DNA (cfDNA) present in the peripheral blood (PB) plasma of patients as a biomarker for MM relapse. RESULTS: We identified several driver mutations by combined analysis of next-generation sequencing and existing databases of candidate oncogenes. Furthermore, relapse was detected more sensitively by monitoring the circulating cfDNA with these driver mutations than by conventional serum free-light chain examination. CONCLUSION: These results suggest the potential utility of cfDNA in the PB plasma of patients as a relevant early biomarker for MM relapse.
BACKGROUND:Multiple myeloma (MM) is an incurable hematological malignancy. Despite the introduction of several novel drugs, most patients relapse. Biomarkers to identify the early signs of relapse will make it possible to adjust the therapeutic strategy before the disease worsens. Although understanding genetic changes is important for the treatment of MM, currently known biomarkers of relapse, including serum free-light chains and monoclonal paraproteins, are not associated with genetic changes. METHODS: We therefore performed a multicenter study to examine the usefulness of circulating cell-free DNA (cfDNA) present in the peripheral blood (PB) plasma of patients as a biomarker for MM relapse. RESULTS: We identified several driver mutations by combined analysis of next-generation sequencing and existing databases of candidate oncogenes. Furthermore, relapse was detected more sensitively by monitoring the circulating cfDNA with these driver mutations than by conventional serum free-light chain examination. CONCLUSION: These results suggest the potential utility of cfDNA in the PB plasma of patients as a relevant early biomarker for MM relapse.
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