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DNA METHYLATION AS A TARGET FOR DIAGNOSIS AND TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
DNA METHYLATION AS A TARGET FOR DIAGNOSIS AND TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
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机译:DNA甲基化作为慢性淋巴细胞白血病(CLL)诊断和治疗的目标
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摘要
Global DNA methylation is a predictor of aggressive disease in patients with chronic lymphocytic leukemia. The higher the DNA methylation, the more likely a patient is going to require systemic therapy. Although there is a gradual decline in global DNA methylation with increasing age in normal individuals, the methylation index only decreases by approximately 0.03 per decade. A pilot study was performed in which patients with chronic lymphocytic leukemia were treated with low doses of DNA methylation inhibitors to evaluate if inhibition of DNA methylation can translate into a clinical benefit. Inhibition of DNA methylation was observed to lead to re-expression of tumor suppressors and normal cellular function. At low non-toxic doses of 0.05-0.09 mg per kilogram per day for three days every 28 days, some patients with chronic lymphocytic leukemia were observed to achieve a reduction in circulating leukemia cells. This was observed to correlate with a reduction in global DNA methylation and an alteration in methylation of core histones.
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