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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.

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.
AuthorsJun 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
JournalAnnals of hematology (Ann Hematol) Vol. 92 Issue 4 Pg. 459-69 (Apr 2013) ISSN: 1432-0584 [Electronic] Germany
PMID23262795 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimetabolites, Antineoplastic
  • Decitabine
  • Azacitidine
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic (therapeutic use)
  • Azacitidine (analogs & derivatives, therapeutic use)
  • Chromosome Mapping (methods)
  • Decitabine
  • Drug Resistance, Neoplasm (genetics)
  • Female
  • Genome, Human (genetics)
  • Humans
  • Karyotyping (methods)
  • Leukemia, Myelomonocytic, Chronic (diagnosis, drug therapy, genetics, mortality)
  • Male
  • Microarray Analysis (methods)
  • Middle Aged
  • Myelodysplastic Syndromes (diagnosis, drug therapy, genetics, mortality)
  • Polymorphism, Single Nucleotide (genetics, physiology)
  • Prognosis
  • Treatment Outcome

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