Figure 3. Analysis of DNA methylation as a tool to detect minimal residual disease.

A. A model of methylation dynamics in ALL. Pretreatment bone marrow of patients with ALL should be populated by two or three clones: a dominant malignant clone (red), residual normal hematopoiesis (black) and potential a subdominant malignant clone (green). With intensive chemotherapy, most patients achieve complete remission and the marrow is now dominated by the normal clone. But because a large fraction of adult patients will relapse with conventional therapy it is possible that residual molecular levels of both the dominant and possibly the subdominant clone are present during remission. At the time of relapse approximately 70% of patients relapse with a methylation pattern similar to that of the initial presentation and 30% with a different profile⁵³. B. Gene specific dynamics of 5 genes at the time of relapse⁵³. Stable indicates that the methylation status of the gene does not change from initial presentation to the time of relapse. C. The data presented in A and B allows the hypothesis that detection of residual levels of methylation at the time of remission could predict worse outcomes. This has been shown for the p73 gene⁵⁴.