High methylation of the 4-aminobutyrate aminotransferase gene predicts a poor prognosis in patients with myelodysplastic syndrome.

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  • Additional Information
    • Source:
      Publisher: D.A. Spandidos Country of Publication: Greece NLM ID: 9306042 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-2423 (Electronic) Linking ISSN: 10196439 NLM ISO Abbreviation: Int J Oncol Subsets: MEDLINE
    • Publication Information:
      Publication: <2003->: Athens, Greece : D.A. Spandidos
      Original Publication: Athens, Greece : Lychnia,
    • Subject Terms:
      Prognosis*; DNA Methylation/*genetics ; Leukemia, Myeloid, Acute/*genetics ; Myelodysplastic Syndromes/*genetics; Adult ; Aged ; Aged, 80 and over ; Apoptosis/genetics ; Disease Progression ; Disease-Free Survival ; Female ; Hemoglobins/metabolism ; Humans ; Karyotype ; Leukemia, Myeloid, Acute/blood ; Leukemia, Myeloid, Acute/pathology ; Male ; Middle Aged ; Myelodysplastic Syndromes/blood ; Myelodysplastic Syndromes/pathology
    • Abstract:
      In our previous study, the 4‑aminobutyrate aminotransferase (ABAT) gene was screened and selected as a target gene that may affect the prognosis of myelodysplastic syndrome (MDS). The present study aimed to determine the prognostic value of ABAT in 152 patients with MDS, 29 patients with acute myeloid leukemia (AML) and 40 controls, by detecting the expression and methylation levels of the ABAT gene. In patients with MDS, the expression levels of ABAT were significantly reduced compared with in the controls (P<0.0001), and the degree of DNA methylation was increased in MDS subjects (P<0.0001). Age, hemoglobin level, marrow blasts, International Prognostic Scoring System karyotype, and the expression and methylation levels of ABAT were associated with overall survival (OS), as determined by univariate analysis. Multivariate analysis revealed that older age, higher marrow blasts and higher methylation percentage were independent risk factors for OS. In addition, a functional study demonstrated that ABAT gene silencing increased cell apoptosis and blocked the G1/S phase in SKM‑1 and THP‑1 human leukemia cells. A γ‑aminobutyrate aminotransferase inhibitor also blocked the G1/S phase; however, it had no effect on cell apoptosis. In conclusion, the present study demonstrated that ABAT methylation served an essential role in the progression of MDS and therefore may be considered an indicator of poor prognosis for hematological malignancies.
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    • Contributed Indexing:
      Keywords: ABAT gene; DNA methylation; overall survival; myelodysplastic syndrome
    • Accession Number:
      0 (Hemoglobins)
    • Publication Date:
      Date Created: 20181212 Date Completed: 20190401 Latest Revision: 20211201
    • Publication Date:
      20221213
    • Accession Number:
      PMC6317695
    • Accession Number:
      10.3892/ijo.2018.4652
    • Accession Number:
      30535457