Clinical implications of telomerase activity levels in acute leukemia.
In the present study, we used the telomeric repeat amplification protocol assay, an internal telomerase assay standard, and an automatic DNA sequencer to detect and quantitate telomerase activity in blood samples obtained from normal and acute leukemia patients. Telomerase activity was analyzed in 78 acute leukemia patients and ranged from 0.65 to 147 relative to the internal standard. Compared to the age-matched normal levels of telomerase activity in the peripheral blood cells, we determined that 45 (81.8%) of 55 acute myeloid leukemia (AML) and 16 (69.6%) of 23 acute lymphoid leukemia patients had elevated telomerase activity. There was no relationship between peak telomere length and telomerase activity in both acute lymphoid leukemia and AML patients. In AML, the level of telomerase activity was associated with French-American-British subtypes and cytogenetics, and patients with elevated telomerase activity had high leukocyte counts and more frequent extramedullary involvement during the disease. Among 78 patients, 5 had high levels of telomerase activities similar to immortalized leukemia cell lines; these 5 patients had a very poor prognosis (P < 0.05). The levels of telomerase activity significantly decreased in patients in complete remission. Most of the patients in complete remission showed a normal level of telomerase activity; however, two of them had low to moderate telomerase activity, and they relapsed shortly after entering complete remission. In relapsed patients, there is a general trend for increased telomerase levels, and 2 of the 13 patients retained high telomerase activity, whereas the other 11 had normal to moderate telomerase activity. These results suggest that telomerase activity may be a useful additional method for monitoring the disease condition in acute leukemia patients.
Ohyashiki
J H
JH
First Department of Internal Medicine, Tokyo Medical College, 6-7-1 Nishi-shinjuku, Shinjuku-ju, Tokyo 160, Japan.
Ohyashiki
K
K
Iwama
H
H
Hayashi
S
S
Toyama
K
K
Shay
J W
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D001331:Automation; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001853:Bone Marrow / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D007223:Infant; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D019098:Telomerase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; D019098:Telomerase