title: [Hypermethylation of CpG island in promoter region of MEIS1 gene and its expression in HOX11(+) acute T lymphoblastic leukemia].
abstract: OBJECTIVE
  To detect the status of methylation in promoter region of MEIS1 gene and its expression in cell lines and patients with HOX11(+) T-cell acute lymphoblastic leukemia (T-ALL) and explore the relationship between the expression level of MEIS1 gene and methylation of CpG island in promoter region.
  
  
  METHODS
  The methylation pattern in MEIS1 gene was detected with bisulfite sequencing PCR, DNA methylation immunoprecipitation and promoter oligonucleotide microarray. And the expression level of MEIS1 mRNA was detected with reverse transcription PCR in 3 T-ALL cell lines: sil-ALL, DND41 and RPMI as well as in 75 clinical bone marrow samples including 38 de novo T-ALL patients, 29 complete remission T-ALL patients and 8 normal samples from January 2009 to December 2011.
  
  
  RESULTS
  The expressions of HOX11 mRNA in the patients were classified into high expression (HOX11(+)) groups (n = 14) and low expression (HOX11(-)) groups (n = 24) . There was hypermethylation of CpG island in promoter region of MEIS1 gene in patients with HOX11(+) T-ALL. The methylation rate of promoter CpG islands of MEIS1 gene in HOX11(+) T-ALL (76.8%) was significantly higher than that of HOX11(-) T-ALL (29.5%) (P < 0.01). The expression MEIS1 in complete remission T-ALL patients and normal samples was significantly lower than that in de novo T-ALL patients (both P < 0.05) . The expression MEIS1 in HOX11(+) cell lines was significantly lower than that in HOX11(-) cell lines (0.392 ± 0.226,0.378 ± 0.317 vs 1.059 ± 0.533, both P < 0.05) and the expression level of MEIS1 in HOX11(+) T-ALL patients (0.462 ± 0.281) significantly lower than that in HOX11(-) T-ALL patients (0.916 ± 0.437) (P < 0.01). The relationship between MEIS1 and HOX11 mRNA expression level had a negative correlation (rs = -0.416, P < 0.01) . The expression level of MEIS1 gene was negatively correlated with the methylation of CpG island in promoter region in T-ALL (rs = -0.383, P < 0.01) .
  
  
  CONCLUSIONS
  The expression of MEIS1 becomes down-regulated or even lost by promoter methylation in T-ALL. HOX11 maybe a negative regulator of MEIS1 gene.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China. Email: jiajinsong@medmail.com.cn.
authors.forename: Jin-song
authors.initials: JS
authors.lastname: Jia
authors.forename: Salvatore
authors.initials: S
authors.lastname: Spicuglia
mesh_terms: D000293:Adolescent; D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C071250:TLX1 protein, human