Association of Leukemia Target Genes Tet2, Bcl2, and Slc23a2 in Vitamin C Pathways

Cancer Genomics Proteomics. 2019 Sep-Oct;16(5):333-344. doi: 10.21873/cgp.20138.

Abstract

Background: Vitamin C has been used in combination with several target genes in the treatment of leukemia. Tet methylcytosine dioxygenase (Tet2), B-cell lymphoma 2 (Bcl2), and solute carrier family 23 member 2 (Slc23a2) are the major target genes in the treatment of leukemia and are relevant to vitamin C.

Materials and methods: Using whole-genome expression profiles from mouse livers, the expression quantitative trait locus (eQTL), correlation matrix, and gene network graph were constructed with probes from each of these three genes and with their relative genes. The function of key genes was examined by their pathways and reported information. The results indicated that although direct correlations among their expression levels were not strong, alternative connecting pathways were discovered. By comparing the expression levels of one probe with known sequences from each of the three genes, we identified several key genes, induced myeloid leukemia cell differentiation protein (Mcl1), far upstream element-binding protein 1 (Fubp1), and tumor protein D52-like 2 (Tpd52l2), which play important roles in acute lymphocytic leukemia and acute myelocytic leukemia. In conclusion, Alternative pathways and key genes that connect Tet2, Bcl2, and Slc23a2 for their therapeutic applications with vitamin C were identified.

Keywords: Vitamin C; alternative pathways; eQTL mapping; key genes; leukemia.

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology*
  • DNA-Binding Proteins / genetics*
  • Dioxygenases
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics
  • Liver / physiology
  • Mice
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Quantitative Trait Loci
  • RNA-Binding Proteins / genetics
  • Sodium-Coupled Vitamin C Transporters / genetics*

Substances

  • DNA-Binding Proteins
  • Mcl1 protein, mouse
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA-Binding Proteins
  • Slc23a2 protein, mouse
  • Sodium-Coupled Vitamin C Transporters
  • fubp1 protein, mouse
  • Bcl2 protein, mouse
  • Dioxygenases
  • Tet2 protein, mouse
  • Ascorbic Acid