Amplification of hTERT and hTERC genes in leukemic cells with high expression and activity of telomerase.
Reactivation of telomerase plays an important role in carcinogenesis. Malignant cells almost always possess high activity and expression of telomerase. The aim of this study was to see whether there is any relationship between telomerase activity and expression and hTERT and hTERC gene amplification in acute lymphoblastic leukemia (ALL) and non-lymphoblastic leukemia (ANLL) cells. In addition telomere length was tested in leukemic cells at the time of diagnosis and during remission. Expression of the three components of telomerase (hTERT, hTERC and TP1) as well as telomerase activity was found both in ALL and ANLL cells. Telomerase activity was diminished in patients in remission. The leukemic cells showed considerable heterogeneity of terminal restriction fragments, that is telomere length. ALL cells showed a variable pattern of telomere length in contrast to ANLL cells which produced a predominantly short telomere pattern. Telomere length in the lymphocytes of leukemia patients was shorter in remission as compared to the time of diagnosis. FISH analysis revealed amplification of hTERT and hTERC genes in ALL and ANLL cells. Quantitative analysis showed that leukemic cells possess higher number of hTERT and hTERC copies than the normal PBL. Our results suggest that the activation of telomerase in leukemic cells is connected with amplification of hTERT and hTERC genes. The high expression and activity of telomerase found in leukemic cells may be partially explained by amplified hTERT and hTERC genes. Amplification of the telomerase genes seems to be a common event in carcinogenesis and may play a role in telomerase reactivation leading to cell immortalization.
Nowak
Tomasz
T
Institute of Human Genetics PAN, Poznan, Poland. nowakjs@man.poznan.pl
Januszkiewicz
Danuta
D
Zawada
Mariola
M
Pernak
Monika
M
Lewandowski
Krzysztof
K
Rembowska
Jolanta
J
Nowicka
Karina
K
Mankowski
Przemyslaw
P
Nowak
Jerzy
J
D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology* / Q000235:genetics; D012313:RNA / Q000235:genetics*; D012074:Remission Induction; D019098:Telomerase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase