Telomerase and the benign and malignant megakaryoblastic leukemias of Down syndrome.

The most common form of leukemia in Down syndrome patients is megakaryoblastic leukemia. There are two forms of the disease. Transient leukemia (TL) is a form of megakaryoblastic leukemia that occurs in newborns with Down syndrome and usually disappears spontaneously within the first 3 months of life. Acute megakaryoblastic leukemia (AMKL) occurs in Down syndrome children within the first 4 years of life and is fatal without treatment. The megakaryoblasts of TL and AMKL are indistinguishable by light and electron microscopy; yet, TL is benign and AMKL is malignant. One of the hallmarks of many malignancies is the expression of telomerase. It is therefore hypothesized that the transient, benign form of megakaryoblastic leukemia (TL) would not contain telomerase activity, whereas telomerase would be demonstrable in the malignant form of the disease. Telomerase activity was determined in the blood and/or bone marrow aspirates in 29 cases of AMKL and 34 cases of TL. The authors found telomerase activity in 15 of 29 (52%) cases, of AMKL and in only 4 of 34 (12%) cases of TL (P < 0.001). Furthermore, three of the four telomerase-positive TL cases were particularly severe, of which two were fatal. Telomerase activity is found frequently in the leukemic cells of the malignant form of megakaryoblastic leukemia but rarely in the benign form of the disease (TL). Observations provide evidence that telomerase may be a critical factor for the malignant conversion of leukemic cells.