ADAM28 overexpression regulated via the PI3K/Akt pathway is associated with relapse in de novo adult B-cell acute lymphoblastic leukemia.
B-cell acute lymphoblastic leukemia (B-ALL) in adults is a very challenging disease. Relapse following remission after induction chemotherapy remains the major barrier to patient survival. ADAM28 is overexpressed in several human tumors and is related to cell proliferation and lymph node metastasis. To date, no information has been available on the prognostic role of ADAM28 in B-ALL. Fifty consecutive patients with de novo B-ALL and 22 healthy donors were enrolled in this study and were followed for 2.8 years. Our data suggested that ADAM28 expression in B-ALL patients was significantly increased (P<0.0001). Patients experiencing disease relapse exhibited significantly increased ADAM28 expression, compared with those with favorable outcomes (P=0.0094). Notably, ADAM28 overexpression was associated with lower probabilities of relapse-free survival (RFS) and event-free survival (EFS) (P<0.001) and was a significant prognostic factor (P<0.001). In vitro, the PI3K/Akt pathway inhibitor, as well as arsenic trioxide (ATO), down-regulated ADAM28 expression. Our results were the first to indicate that ADAM28 overexpression in B-ALL patients is correlated with relapse. ADAM28 overexpression is potentially regulated by the PI3K/Akt pathway. These data demonstrate that ADAM28 might serve as a novel biomarker for evaluating relapse in B-ALL and as a potential therapeutic target in B-ALL patients.
Peking University People's Hospital, Peking University Institute of Hematology, PR China. Electronic address: zhangxh100@sina.com.
Xiao-Hui
XH
Zhang
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Chen-Cong
CC
Wang
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Qian
Q
Jiang
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Shen-Miao
SM
Yang
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Hao
H
Jiang
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Jin
J
Lu
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Qian-Ming
QM
Wang
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Fei-Er
FE
Feng
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Xiao-Lu
XL
Zhu
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Ting
T
Zhao
Peking University People's Hospital, Peking University Institute of Hematology, PR China.
Xiao-Jun
XJ
Huang
ADAM28; B-cell acute lymphoblastic leukemia; PI3K/Akt pathway; Prognosis