Enhanced ALOX12 Gene Expression Predicts Therapeutic Susceptibility to 5-Azacytidine in Patients with Myelodysplastic Syndromes.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Myelodysplastic Syndromes*/genetics ; Myelodysplastic Syndromes*/drug therapy ; Azacitidine*/therapeutic use ; Azacitidine*/pharmacology ; DNA Methylation*/drug effects ; Arachidonate 12-Lipoxygenase*/genetics ; Arachidonate 12-Lipoxygenase*/metabolism; Humans ; Male ; Female ; Aged ; Middle Aged ; Aged, 80 and over ; Adult
    • Abstract:
      5-azacytidine (AZA), a representative DNA-demethylating drug, has been widely used to treat myelodysplastic syndromes (MDS). However, it remains unclear whether AZA's DNA demethylation of any specific gene is correlated with clinical responses to AZA. In this study, we investigated genes that could contribute to the development of evidence-based epigenetic therapeutics with AZA. A DNA microarray identified that AZA specifically upregulated the expression of 438 genes in AZA-sensitive MDS-L cells but not in AZA-resistant counterpart MDS-L/CDA cells. Of these 438 genes, the ALOX12 gene was hypermethylated in MDS-L cells but not in MDS-L/CDA cells. In addition, we further found that (1) the ALOX12 gene was hypermethylated in patients with MDS compared to healthy controls; (2) MDS classes with excess blasts showed a relatively lower expression of ALOX12 than other classes; (3) a lower expression of ALOX12 correlated with higher bone marrow blasts and a shorter survival in patients with MDS; and (4) an increased ALOX12 expression after AZA treatment was associated with a favorable response to AZA treatment. Taking these factors together, an enhanced expression of the ALOX12 gene may predict favorable therapeutic responses to AZA therapy in MDS.
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    • Grant Information:
      21K06703 Japan Society for the Promotion of Science
    • Contributed Indexing:
      Keywords: 5-azacytidine; ALOX12; myelodysplastic syndromes
    • Accession Number:
      M801H13NRU (Azacitidine)
      EC 1.13.11.31 (Arachidonate 12-Lipoxygenase)
      EC 1.13.11.31. (ALOX12 protein, human)
    • Publication Date:
      Date Created: 20240511 Date Completed: 20240511 Latest Revision: 20240610
    • Publication Date:
      20240610
    • Accession Number:
      PMC11083213
    • Accession Number:
      10.3390/ijms25094583
    • Accession Number:
      38731802