and Methylation Changes in the Bone Marrow of Acute Myeloid Leukemia Patients During Chemotherapy

Aberrant promoter DNA methylation is a major mechanism of leukemogenesis in hematologic malignancies, including acute myeloid leukemia (AML). However, the association between promoter methylation with chemotherapeutic outcomes remains unknown. In the present study, bone marrow samples were collected prior to and following chemotherapy in 30 AML patients. Methylation-specific polymerase chain reaction technology was used to examine the promoter methylation status of adenomatous polyposis col 2 () and cytochrome P450 family 1 subfamily B polypeptide 1 (). The results revealed no change in the methylation status of the promoter in patients following various chemotherapy regimens. However, the methylation status of the promoter changed in response to 6 different chemotherapy regimens. AML patients of the M3 subtype displayed an induction of the promoter methylation levels more frequently (57.1%) than patients affected by the other subtypes (M1: 33.3%; M2: 12.5%; M4: 16.7%; M5: 0% and M6: 0%). In addition, a higher frequency of male patients (4/13) exhibited modulation of the promoter methylation status compared with female patients (3/17). Furthermore, of five AML patients with a poor prognosis, two exhibited changes leading to hypomethylation and two leading to hypermethylation. By contrast, three other patients exhibited hypermethylation changes along with remission. This may be explained by the different chemotherapy regimens used to treat these patients or by other unknown factors. The present study revealed that promoter methylation was induced during chemotherapy, whereas the promoter remained hemimethylated. Furthermore, the changes in methylation were dependent on the AML subtypes and the gender of the patients.