title: Decreased gene expression for telomeric-repeat binding factors and TIN2 in malignant hematopoietic cells.
abstract: BACKGROUND
  Details of mechanisms regulating telomere length are poorly understood in human hematopoietic cells.
  
  
  METHODS
  Gene expression for TRFs and TIN2 was studied in hematopoietic cell lines, blood or bone marrow cells from acute leukemia and in normal leukocyte fractions.
  
  
  RESULTS
  The telomeres were longest in normal leukocytes, shorter in patient samples and still shorter in malignant hematopoietic cell lines. TRF1 mRNA, TRF2 mRNA and TIN2 mRNA in three myeloblastic cell lines and six lymphoblastic cell lines were significantly less abundant than in the corresponding normal cell types. In patients with acute myeloid leukemia, expression of these gene was also less than in normal cells. In additional studies in culture, HL-60 cells with initially high telomerase activity and low expression of TRF mRNA and TIN2 mRNA differentiated into granulocytic and monocytic cells with low telomerase activity and high expression of these mRNAs.
  
  
  CONCLUSIONS
  In hematopoietic carcinogenesis, gene expression for suppressors of telomerase activity, such as TRF and TIN2, is decreased. These genes might hold promise for gene therapy against cancer.
authors.affiliation: Division of Laboratory Diagnosis, Sapporo Medical University School of Medicine, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamada
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Yagihashi
authors.forename: Mikako
authors.initials: M
authors.lastname: Yamada
authors.forename: Koichi
authors.initials: K
authors.lastname: Asanuma
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Moriai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsuji
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018922:HL-60 Cells; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D019098:Telomerase