methylation correlates with disease progression in patients with chronic myeloid leukemia.

Background: Our previous study has reported that aberrant methylation was associated with poor prognosis in AML, and it correlated with disease progression in MDS. Herein, we further determined methylation and its clinical significance in the other myeloid malignance - chronic myeloid leukemia (CML).

Methods: methylation was examined by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR, whereas expression was detected by real-time quantitative PCR.

Results: methylation was identified in 11% (10/95) CML patients. methylation was associated with lower hemoglobin and platelets (=0.006 and 0.032, respectively). Importantly, significant differences were observed in the distributions of clinical stages and cytogenetics (=0.006 and 0.002, respectively). The frequency of methylation in chronic phase (CP) stage occurred with lowest frequency (4/74, 5%), higher in accelerated phase (AP) stage (1/7, 14%), and the highest in blast crisis (BC) stage (12/31, 39%). In addition, methylated patients tended to have a higher level of transcript than non-methylated patients (=0.063). In two paired CML patients, methylation showed lower density in CP stage (19% and 17%, respectively), and was significantly increased in BC stage (89% and 69%, respectively) during disease progression. Additionally, methylated CML patients presented a lower transcript level than non-methylated CML patients (=0.046).

Conclusion: Our study revealed that methylation correlated with disease progression in chronic myeloid leukemia.