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TELOMERASE ACTIVITY AS EARLY DETECTION OF LEUKEMIA IN PEDIATRIC PATISNTS WHO INITIALLY DIASNOSED APLASTIC ANAEMIA

Leland Reniarti, P.H. Achmad, A.M. Maskoen

Department of Child Health Medical School Padjadjaran University-Hasan

Sadikin Hospital, Bandung, Indonesia.

Telomerase activation is important for carcinogenesis, Higher telomerase activity was detected in patients with cancer including children with lonkemis, Preleukem c state remains a diagnostic problem Patient who is initially diagnosed as Aplastic anemia but after several weeks or months become leukemia (ALL or AML) is considered as preloukemia. The aim of this study was to find out whether patients with aplastie anaemia who become leukemia have bed higher telomerase activity as the time they were diagnosed as apdastic anaemia. We analyzed telomerase activity in leukocytes taken from ponipheral blood (PB) specimens of the subjects at the time they were diagnosed. Subjects were all pediatric patients who were diagnosed as leukemia or aplastic anaemia between the period of January-December 1999. For comparative analysis PII specimens from healthy children were analyzed. Telomerase activity was detected using telomeric Repeat Amplification Protocol (TRAP) assay. Patients who are diagnosed as aplastic anaemia were followed up clinically for 6 months for the possibility to develop leukemia, The data was analyzed using chi-square analysis. The mean value of telomerase activity found specimens with mean value 0.31 u/2 million cells Higher telomerase activity was detected in almost all 21 pediatric patient: with leukemia (1) ALL, 9 AML, 1 CML) with mean value 0.88 (range 0.01-2.34). However heterogenicity of telomerase activity was found amongst this group. Among 14 patients diagnosed as aplastie anaemia at the first time of diagnosis, 6 remained aplastie anaemia, while 8 became leukemia (preleukemia), Surprisingly, high telomerase activity was detected in these patients with mean value was 1.69 (range 0.46-6.24). Aplastie anaemia patients who have had increased telomerase activity were considered to be at risk to develop leukemia 2.3 fold (p=0.017). There were no association between telomerase activity and clinical manifestation of hepato-splenomegaly and lymphadenopathy, but significant association was found between high telomerase activity (0.31) and leucoeyte cont >100.000/mm3. We suggested that telomerase activity might be a useful diagnosis for early detection of the possibility to become leukemia in pediatric patients who were initially diagnosed as aplastic anacmia, and might improve therapy and prognostic factor The use of telomerase inhibitors may provide an effective adjunct to the therapy of leukemia and prelcukcmia.