Telomerase activity and telomere length in patients with acute promyelocytic leukemia: indicative of proliferative activity, disease progression, and overall survival.
BACKGROUND
The progressive shortening of telomeres and the activation of telomerase have been considered to be one of the key mechanisms in cellular immortalization and tumor progression.


METHODS
About 300 sequential samples were collected from 40 patients during the course of acute promyelocytic leukemia (APL) disease. Telomerase activity (TA) and terminal restriction fragment (TRF) length were assessed by TRAP and Southern blot analyses, respectively. PML-retinoic acid receptor alpha (RARa)/glucose-6-phosphate dehydrogenase transcripts were quantified by real-time PCR.


RESULTS
About 90% of the patients had a significant reduction in telomere length (TL) relative to the control (median 3.5 versus 11.37 kbp; P < 0.001). A significant positive correlation between TL and PML-RARa expression was found (P = 0.001). Telomerase was activated in all patients; however, TA level was significantly higher in the group of relapsed patients than patient with newly diagnosed. The group of patients with shortened TRF and elevated TA had a significantly poorer overall survival.


CONCLUSIONS
The shortened TL and elevated TA in APL patients are mainly indicative of extensive proliferative activity and they correlate with disease progression and relapse; thus, they may serve as prognostic factors for a subset of APL patients with more aggressive disease and poor outcome, those who may not respond favorably to arsenic therapy.
Ghaffari
S H
SH
Hematology, Oncology and BMT Research Center, Tehran University Medical Sciences, Tehran, Iran. shghaffari2000@yahoo.com
Shayan-Asl
N
N
Jamialahmadi
A H
AH
Alimoghaddam
K
K
Ghavamzadeh
A
A
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D018450:Disease Progression; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis; D010087:Oxides / Q000627:therapeutic use; D015996:Survival Rate; D019098:Telomerase / Q000097:blood*; D016615:Telomere / Q000187:drug effects / Q000378:metabolism*
D000970:Antineoplastic Agents; D001152:Arsenicals; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D019098:Telomerase; D000077237:Arsenic Trioxide