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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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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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Acknowledgments

This study was supported by grants of Korea Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A090618 and A100821) and a grant of the National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea (A111218-GM06).

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The authors declare that they have no conflict of interest.

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Correspondence to Hyeoung-Joon Kim or Dennis Dong Hwan Kim.

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Supplemental Table 1

Summary of abnormal SNP lesions identified by genome-wide SNP array-based karyotyping (DOCX 36 kb)

Supplemental Table 2

Summary of abnormal SNP lesions in individual cases with normal karyotype by metaphase analysis (DOC 58 kb)

Supplemental Figure 1

Result of metaphase cytogenetics and SNP-A karyotyping (A, metaphase cytogenetics; B, SNP-A karyotyping; C, combined (any abnormality detected by either method was considered as abnormal) (no. of patients, percent) (DOC 63 kb)

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Yi, J.H., Huh, J., Kim, HJ. et al. Genome-wide single-nucleotide polymorphism array-based karyotyping in myelodysplastic syndrome and chronic myelomonocytic leukemia and its impact on treatment outcomes following decitabine treatment. Ann Hematol 92, 459–469 (2013). https://doi.org/10.1007/s00277-012-1635-7

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  • DOI: https://doi.org/10.1007/s00277-012-1635-7

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