title: Simultaneous detection of MDR1 and WT1 gene expression to predict the prognosis of adult acute lymphoblastic leukemia.
abstract: The interaction between Wilms tumor gene 1 (WT1) and the promoter region of the multidrug resistance-1 (MDR1) gene has been previously reported but the clinical significance of the coexpression of WT1 and MDR1 in acute lymphoblastic leukemia (ALL) is still largely unknown. In this study, the expression levels of WT1 and MDR1 mRNA in 57 adult ALL patients were simultaneously detected using multiplex fluorescence real-time quantitative polymerase chain reaction. The expression levels of WT1 and MDR1 in bone marrow samples of adult ALL patients were significantly higher than those in the normal samples (P<0.001), and in addition, the expression levels of WT1 and MDR1 mRNA were highly correlated (r(s)=0.404, P=0.002). According to the expression levels of these two genes, the patients in this study were subdivided into the following three groups: low-WT1/low-MDR1 (n=16), high-WT1 or high-MDR1 (n=24), high-WT1/high-MDR1 (n=17). There was no significant difference in response to induction therapy among these three cohorts (P=0.217). The overall first year relapse rate was 53.2% (25 out of 47 ALL patients). High-WT1/high-MDR1 mRNA expression was strongly associated with BCR-ABL expression and a higher tendency to be T-cell ALL type. In addition, high-WT1/high-MDR1 have a significantly higher relapse rate (P=0.048) and shorter disease free survival (P=0.016). Our data suggests that high-WT1/high-MDR1 levels of mRNA expression may be associated with relatively poorer outcomes in patients with ALL. Therefore, the expression of WT1 and MDR1 may provide useful information for clinical decision.
authors.affiliation: Department of Hematology, Nanfang Hospital, The Southern Medical University, Guangzhou 510515, China. xubingzhangjian@126.com
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Song
authors.forename: Nga Chi
authors.initials: NC
authors.lastname: Yip
authors.forename: Pingnan
authors.initials: P
authors.lastname: Xiao
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.forename: Shuyun
authors.initials: S
authors.lastname: Zhou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D001853:Bone Marrow / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D016162:Genes, Wilms Tumor; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012074:Remission Induction; D014750:Vincristine / Q000008:administration & dosage; D025721:WT1 Proteins / Q000032:analysis* / Q000096:biosynthesis; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025721:WT1 Proteins; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008727:Methotrexate