Telomerase activity in plasma cell dyscrasias.
Activation of telomerase is essential for in vitro cellular immortalization and tumorigenesis. In the present study, we investigated telomerase activation and its implications in plasma cell dyscrasias including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plasma cell leukaemia (PCL). All 5 patients with MGUS exhibited normal levels of telomerase activity in their plasma cells. Elevated telomerase activity was found in the samples from 21/27 patients with MM and 4/4 with PCL. In addition, 4 myeloma cell lines all expressed high levels of telomerase activity. The expression of telomerase reverse transcriptase (hTERT) and telomerase RNA template (hTER) was positively associated with the levels of telomerase activity in MM/PCL. Tankyrase expression was upregulated, concomitant with the induction of hTERT and activation of telomerase in MM/PCL. The present findings indicate that MGUS cells may not be immortalized and that activation of telomerase plays a role in the malignant transformation from MGUS to MM.
Department of Medicine, Division of Hematology, Karolinska Hospital, SE-171 76, Stockholm, Sweden.
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D
Xu
C
C
Zheng
S
S
Bergenbrant
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G
Holm
M
M
Björkholm
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Yi
A
A
Gruber
D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000201:enzymology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D006801:Humans; D007952:Leukemia, Plasma Cell / Q000201:enzymology / Q000209:etiology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000201:enzymology / Q000209:etiology*; D010265:Paraproteinemias / Q000201:enzymology*; D010950:Plasma Cells / Q000201:enzymology; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D012313:RNA; D038501:Tankyrases; D019098:Telomerase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D011065:Poly(ADP-ribose) Polymerases; D012313:RNA; D038501:Tankyrases; D019098:Telomerase; C422952:telomerase RNA; C418109:TNKS protein, human