Abnormal regional hypermethylation of the calcitonin gene in myelodysplastic syndromes.

Abnormal regional hypermethylation of the calcitonin gene can be detected in up to 95% of patients with acute nonlymphocytic leukemia (ANLL). We used a polymerase chain reaction (PCR) based assay to detect abnormal regional hypermethylation at this locus in patients with primary myelodysplastic syndromes (MDS). Hypermethylation was detected in 13 of 20 patients (65%) with MDS and was detected in nine patients with MDS and normal cytogenetics. There was no correlation between detection of this abnormality and the subtype of MDS. Four of the 13 patients (30%) with abnormal methylation have progressed to ANLL with a median time to progression of 3.5 months. The actuarial median survival of the cohort with abnormal methylation was 17 months, while that of the cohort with normal methylation is not yet reached. These preliminary findings suggest that detection of abnormal methylation at this locus may be useful as a diagnostic tool in MDS. Furthermore, hypermethylation of the calcitonin gene may be a poor prognostic feature that predicts progression to acute leukemia in patients with primary MDS.