ADAM28 overexpression regulated via the PI3K/Akt pathway is associated with relapse in de novo adult B-cell acute lymphoblastic leukemia

作者：Zhang, Xiao-Hui^*; Wang, Chen-Cong; Jiang, Qian; Yang, Shen-Miao; Jiang, Hao; Lu, Jin; Wang, Qian-Ming; Feng, Fei-Er; Zhu, Xiao-Lu; Zhao, Ting; Huang, Xiao-Jun

来源：Leukemia Research, 2015, 39(11): 1229-1238.

DOI：10.1016/j.leukres.2015.08.006

• B-cell acute lymphoblastic leukemia
• ADAM28
• Prognosis
• PI3K/Akt pathway

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. ADA1VI28 is over-expressed 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.

• 出版日期2015-11
• 单位北京大学