title: APC2andCYP1B1methylation changes in the bone marrow of acute myeloid leukemia patients during chemotherapy.
abstract: 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 (APC2) and cytochrome P450 family 1 subfamily B polypeptide 1 (CYP1B1). The results revealed no change in the methylation status of theAPC2promoter in patients following various chemotherapy regimens. However, the methylation status of theCYP1B1promoter changed in response to 6 different chemotherapy regimens. AML patients of the M3 subtype displayed an induction of theCYP1B1promoter 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 theCYP1B1promoter methylation status compared with female patients (3/17). Furthermore, of five AML patients with a poor prognosis, two exhibited changes leading toCYP1B1hypomethylation and two leading toCYP1B1hypermethylation. 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 thatCYP1B1promoter methylation was induced during chemotherapy, whereas theAPC2promoter remained hemimethylated. Furthermore, the changes inCYP1B1methylation were dependent on the AML subtypes and the gender of the patients.
authors.affiliation: Department of Hematology, Yuyao People's Hospital, Ningbo University Yangming Affiliated Hospital, Yuyao, Zhejiang 315400, P.R. China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Qingxiao
authors.initials: Q
authors.lastname: Hong
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Huadan
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Hematology, Yuyao People's Hospital, Ningbo University Yangming Affiliated Hospital, Yuyao, Zhejiang 315400, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Fang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Annan
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Danjie
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
keywords: acute myeloid leukemia; adenomatous polyposis col 2; chemotherapy; cytochrome P450 family 1 subfamily B polypeptide 1; promoter methylation