ADAM28 overexpression regulated via the PI3K/Akt pathway is associated with relapse in de novo adult B-cell acute lymphoblastic leukemia. Issue 11 (November 2015)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Leukemia research. Volume 39:Issue 11(2015:Nov.)
• Page Start: 1229
• Page End: 1238
• Publication Date: 2015-11
• Subjects: B-ALL B-cell acute lymphoblastic leukemia -- ATO arsenic trioxide -- ADAMA disintegrin and metalloproteinases -- RFS relapse-free survival -- EFS event-free survival -- OS overall survival -- CR complete remission -- CNS central nervous system -- ATRA all-trans retinoic acid -- MRD minimal residual disease -- BM bone marrow -- ELISA enzyme-linked immunosorbent assay -- RT-PCR real-time quantitative polymerase chain reaction -- ROC receiver operating characteristics; B-cell acute lymphoblastic leukemia -- ADAM28 -- Prognosis -- PI3K/Akt pathway; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2015.08.006
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: The ADAM28 expression level in relapsed adult B-ALL patients was elevated. The ADAM28 expression level was associated with EFS in de novo adult B-ALL patients. Selective inhibitor could inhibit the ADAM28 expression in primary B-ALL cells. The ADAM28 expression might be regulated via the PI3K/Akt pathway. Abstract: 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.