Accelerated telomere length shortening in granulocytes: a diagnostic marker for myeloproliferative diseases.
OBJECTIVE
The telomere in mature myeloid cells derived from abnormal progenitor cells of myeloproliferative diseases (MPDs) may shorten more rapidly than that in T lymphocytes, which are considered to be derived from normal clones. To test this hypothesis, we measured telomere lengths in granulocytes and T lymphocytes from patients with MPDs and compared them with those from normal individuals.


METHODS
Granulocytes and T lymphocytes were separated from the peripheral blood of 65 patients with MPDs (25 chronic myelogenous leukemia [CML], 16 polycythemia vera, 19 essential thrombocythemia, 5 chronic idiopathic myelofibrosis) and 35 normal individuals. Genomic DNA from each cell fraction was subjected to Southern blot hybridization to determine the mean telomere length.


RESULTS
Telomere lengths in granulocytes from patients with MPDs were significantly shorter than those from normal individuals (vs CML, p = 0.002; vs other MPDs, p < 0.0001). However, there was no statistical difference in telomere length in T lymphocytes between MPD patients and normal individuals (vs CML, p = 0.35; vs other MPDs, p = 0.85). DeltaTRF (terminal restriction fragment) in patients with MPDs, which is defined as the difference in telomere length between granulocytes and T lymphocytes, was significantly longer than that in normal individuals.


CONCLUSIONS
The results support the disease theory that MPDs result from extensive proliferation of myeloid progenitor cells, leading to accelerated telomere length shortening in mature granulocytes. An increase in DeltaTRF over the standard value (>1.74 kb) may be useful for discriminating leukocytosis due to MPDs from reactive leukocytosis.
Terasaki
Yasushi
Y
Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan.
Okumura
Hirokazu
H
Ohtake
Shigeki
S
Nakao
Shinji
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D016022:Case-Control Studies; D005260:Female; D006098:Granulocytes / Q000648:ultrastructure*; D006801:Humans; D007964:Leukocytosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods / Q000592:standards; D009196:Myeloproliferative Disorders / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D013601:T-Lymphocytes / Q000648:ultrastructure; D016615:Telomere / Q000378:metabolism / Q000648:ultrastructure*