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 DNAsderived 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 (p00.002) and showed a trend of worse OS (p00.02 in univariate, p00.09 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. Keywords Myelodysplastic syndrome . Chronic monomyelocytic leukemia . Single nucleotide polymorphism-based karyotyping . Copy number alterations . Copy neutral loss of heterozygosity (CN-LOH)