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Genome-wide single-nucleotide polymorphism array-based karyotyping in myelodysplastic syndrome and chronic myelomonocytic leukemia and its impact on treatment outcomes following decitabine treatment |
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| Authors: | Jun Ho Yi Jungwon Huh Hee-Jin Kim Sun-Hee Kim Sung Hyun Kim Kyoung Ha Kim Young Rok Do Yeung-Chul Mun Hawk Kim Min Kyoung Kim Hyeoung-Joon Kim TaeHyung Kim Dennis Dong Hwan Kim |
| Institution: | 1. Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong 50, Gangnam-gu, Seoul, 135-710, South Korea 2. Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea 3. Department of Laboratory Medicine, Ewha Womans University School of Medicine, Seoul, South Korea 4. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea 5. Department of Hematology/Oncology, DongA University Medical Center, DongA University, Busan, South Korea 6. Department of Hematology/Oncology, Soonchunhyang University Seoul Hospital, Seoul, South Korea 7. Department of Hematology/Oncology, Dongsan Hospital, Keimyung University, Daegu, South Korea 8. Department of Hematology/Oncology, Ewha Womans University School of Medicine, Seoul, South Korea 9. Division of Hematology/Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea 10. Department of Hematology/Oncology, Yeungnam University Medical Center, Daegu, South Korea 11. Department of Hematology/Medical Oncology, Chonnam National University Hwasun Hospital, Chonnam National University, Ilshim-ri 160, Hwasun-eup, Hwasun, 519-763, South Korea 12. Department of Bioinformatics, Donnelley Center, University of Toronto, Toronto, ON, Canada 13. Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada |
| Abstract: | Decitabine is a hypomethylating agent with proven clinical efficacy in myelodysplastic syndrome (MDS). The current study analyzed the role of single nucleotide polymorphism array (SNP-A)-based karyotyping in prediction of clinical outcome in MDS or chronic myelomonocytic leukemia (CMML) patients following decitabine therapy. A total of 61 MDS/CMML patients treated with decitabine were evaluated with Genome-Wide Human SNP 6.0 Array using DNAs derived from marrow samples. The primary endpoint was the best response rate including complete (CR) and partial response (PR) with overall (OS) and event-free survival (EFS) as secondary endpoints. Best response was noted in 14 patients (26.4 %) out of 53 evaluated patients including 12 CR and two PR with median follow-up of 21.6 months. A total of 81 abnormal SNP lesions were found in 25 out of 61 patients (41.0 %). The patients carrying abnormal SNP lesions showed an inferior CR/PR rate (p?=?0.002) and showed a trend of worse OS (p?=?0.02 in univariate, p?=?0.09 in multivariate) compared to those without SNP lesions, but not were associated with inferior EFS. The presence of abnormal SNP lesions in MDS was associated with adverse outcomes following decitabine therapy. Further study is strongly warranted to establish the role of SNP-A karyotyping in MDS. |
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