title: Overexpression of EPS8 is associated with poor prognosis in patients with acute lymphoblastic leukemia.
abstract: Molecular markers have become an invaluable tool in monitoring disease status particularly of leukemias, as bone marrow samples can be easily collected for analysis during all stages of disease development including diagnosis, treatment, and follow-up. Two genes that have been used as prognostic markers in acute leukemia are Wilms' tumor (WT1) and multidrug resistance-1 (MDR1). A novel gene, epidermal growth factor receptor pathway substrate 8 (EPS8), is often over-expressed and associated with poor outcome in some solid tumor types. However, whether EPS8 is also associated with the development of acute lymphoblastic leukemia (ALL) is unclear. Here, quantitative real-time PCR was used to evaluate the expression of EPS8, MDR1, and WT1 in bone marrow samples of adult ALL patients (n=107) and non-leukemia controls (n=22). EPS8, MDR1, and WT1 were detected in ALL patients, and significant correlations were found between expression profiles for EPS8 and MDR1, EPS8 and WT1, and MDR1 and WT1. In general, high expression of EPS8, MDR1, or WT1 in patients was associated with a higher risk of relapse. Furthermore, when patients were stratified based on high or low expression of the genes, Kaplan-Meier survival analysis indicated that disease-free survival of patients with the high-EPS8/high-WT1/high-MDR1 profile was significantly shorter than in patients with the low-EPS8/low-WT1/low-MDR1 profile or those excluded from either of these groups (P<0.0001). Thus, EPS8, as MDR1 and WT1, may be a clinically valuable biomarker for assessing the outcome of ALL patients.
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, China.
authors.forename: Ying-Zhi
authors.initials: YZ
authors.lastname: He
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Second School of Clinical Medicine, Southern Medical University, 510515 Guangzhou, China.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Wu
authors.affiliation: Second School of Clinical Medicine, Southern Medical University, 510515 Guangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, China.
authors.forename: Chao-Yang
authors.initials: CY
authors.lastname: Song
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, China.
authors.forename: Bing-Yi
authors.initials: BY
authors.lastname: Wu
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, China.
authors.forename: San-Fang
authors.initials: SF
authors.lastname: Tu
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, 510282 Guangzhou, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D015996:Survival Rate; D025721:WT1 Proteins / Q000096:biosynthesis
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C489989:EPS8 protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: Acute lymphoblastic leukemia; EPS8; MDR1; Minimal residual disease; WT1; mRNA expression