ABNORMAL REGIONAL HYPERMETHYLATION OF THE CALCITONIN-GENE IN MYELODYSPLASTIC SYNDROMES

Abnormal regional hypermethylation of the calcitonin gene can be detec ted in up to 95% of patients with acute nonlymphocytic leukemia (ANLL) . We used a polymerase chain reaction (PCR) based assay to detect abno rmal regional hypermethylation at this locus in patients with primary myelodysplastic syndromes (MDS). Hypermethylation was detected in 13 o f 20 patients (65%) with MDS and was detected in nine patients with MD S and normal cytogenetics. There was no correlation between detection of this abnormality and the subtype of MDS. Four of the 13 patients (3 0%) with abnormal methylation have progressed to ANLL with a median ti me to progression of 3.5 months, The actuarial median survival of the cohort with abnormal methylation was 17 months, while that of the coho rt with normal methylation is not yet reached. These preliminary findi ngs suggest that detection of abnormal methylation at this locus may b e useful as a diagnostic tool in MDS. Furthermore, hypermethylation of the calcitonin gene may be a poor prognostic feature that predicts pr ogression to acute leukemia in patients with primary MDS.