Hypermethylation of the human calcitonin gene as a molecular marker of acute lymphoblastic leukemia

HpaII/MspI blot-hybridization analysis of the 5'-end region of the calcitonin (CT) gene methylation in cells of bone marrow and peripheral blood of patients with acute lymphoblastic leukemias (ALL) has been carried out. ALLs are accompanied by hypermethylation of the inner cytosine in the CCGG sequences of this region of the CT gene. The level of hypermethylation of the CT gene corresponded to the degree of disease progression and malignancy. At a long-term remission, hypermethylation of the CT gene is not observed. In case of primary resistance or if the complete remission has not been achived the CT gene remained hypermethylated. It has been shown that in relapse the normal CT gene methylation pattern reversed to hypermethylation. This, phenomenon was detected 1-8 months before the obvious clinical and laboratory signs of the disease progression (relapse). The large size of abnormal HpaII-fragments of the 5'-end region of the calcitonin gene had a direct correlation with the malignancy status of ALL.