Gene activity predicts course of chronic leukemia

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A newly identified molecular marker quickly helps to distinguish whether a person with chronic lymphocytic leukemia (CLL) has a more aggressive or less aggressive form of the disease, information that guides treatment decisions.

As John C. Byrd, MD, of the Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Solove Research Institute in Columbus, Ohio, and colleagues noted in Journal of Clinical Oncology (, increased expression of the ZAP-70 gene is known to predict poor prognosis in CLL. However, current methods for accurately measuring ZAP-70 are expensive and difficult to perform.

The investigators used a mass spectroscopy-based technique to analyze DNA methylation of the entire ZAP-70 gene regulatory regions in 247 CLL samples taken from patients participating in four different clinical studies. Methylation influences how much protein is produced by ZAP-70 and other genes. Byrd's group hypothesized that changes in ZAP-70 methylation status could explain decreases in ZAP-70 expression and a more favorable clinical outcome.

The researchers were able to identify a small area in one regulatory region of the ZAP-70 gene that showed large variability in methylation in CLL samples while being universally methylated in normal B cells.

The results demonstrated that patients are likely to have the slow-progressing form of CLL when the ZAP-70 gene is methylated in leukemia cells, and likely to have aggressive disease when the gene is unmethylated. In the latter group of patients, clinicians should consider beginning treatment immediately.     

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