title: 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.
authors.affiliation: 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.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Yi
authors.forename: Jungwon
authors.initials: J
authors.lastname: Huh
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Kyoung Ha
authors.initials: KH
authors.lastname: Kim
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Do
authors.forename: Yeung-Chul
authors.initials: YC
authors.lastname: Mun
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: TaeHyung
authors.initials: T
authors.lastname: Kim
authors.forename: Dennis Dong Hwan
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002874:Chromosome Mapping / Q000379:methods; D000077209:Decitabine; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000502:physiology; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine