Acceleration of chronic myeloid leukemia correlates with calcitonin gene hypermethylation.
Calcitonin gene methylation at CCGG sites were determined in 39 chronic myeloid leukemia patients by isoschizomeric restriction endonuclease analysis. A total of 27 patients were analyzed while still in the chronic phase: 20 patients had a normal gene, and seven had a hypermethylated gene. There were 12 patients initially studied in accelerated or blastic phases. All but one patient showed gene hypermethylation, suggesting a good correlation between gene methylation and disease stage. All five patients who, while still in the chronic phase, had a major 3.1-kb hypermethylated calcitonin gene fragment, accelerated within 2 to 27 months. In consecutively analyzed patients, the initially normal calcitonin gene changed to a hypermethylated state as the disease escalated. The hypermethylation predicted disease acceleration with a median lead time of 6 months before any morphologic or clinical signs of disease progression were seen. The disease progressed in 8 of 27 patients initially studied in the chronic phase: in only two patients this occurred without predictive methylation changes. The results suggest that the assessment of calcitonin gene methylation status may be a promising tool for monitoring chronic myeloid leukemia disease escalation.
Malinen
T
T
Department of Clinical Chemistry, University of Helsinki, Finland.
Palotie
A
A
Pakkala
S
S
Peltonen
L
L
Ruutu
T
T
Jansson
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SE
D014408:Biomarkers, Tumor / Q000032:analysis; D001752:Blast Crisis / Q000175:diagnosis*; D001853:Bone Marrow / Q000473:pathology; D002116:Calcitonin / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011379:Prognosis; D015183:Restriction Mapping
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers; D002116:Calcitonin