Decreased gene expression for telomeric-repeat binding factors and TIN2 in malignant hematopoietic cells.
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.
Yamada
Koji
K
Division of Laboratory Diagnosis, Sapporo Medical University School of Medicine, Japan.
Yagihashi
Atsuhito
A
Yamada
Mikako
M
Asanuma
Koichi
K
Moriai
Ryosuke
R
Kobayashi
Daisuke
D
Tsuji
Naoki
N
Watanabe
Naoki
N
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
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