title: Combinatorial molecular marker assays of WT1, survivin, and TERT at initial diagnosis of adult acute myeloid leukemia.
abstract: High levels of expression of Wilms' tumor gene 1 (WT1), survivin, or telomerase reverse transcriptase (TERT) genes are introduced as leukemia-associated targets predicting clinical outcome. We prospectively investigated the leukemia-associated gene transcripts by real-time quantitative polymerase chain reaction from 151 adult patients with AML associated with the patients' clinical characteristics. The maximum levels of each gene in bone marrow were 64.4-, 8.1-, and 3.9-fold higher than those in the normal control, respectively. In contrast to the WT1 and TERT levels, survivin showed comparatively higher expression in the unfavorable cytogenetic group of patients. We found a significant difference in survivin levels between the CR and non-CR groups (P = 0.0237). TERT expression levels were higher in patients who had a greater number of peripheral blood leukemic blasts at diagnosis (P = 0.0191). Non-MRC subtypes and patients without specific mutations were the most powerful predictive factors for a better CR rate, by multivariate analyses. The lower levels of both WT1 and survivin co-expression (P = 0.0129) and both survivin + TERT co-expression (P = 0.0115) were significant factors for better OS. Besides lower initial levels of serum ferritin (P = 0.0401), lower levels of WT1 (P = 0.0438) and survivin (P = 0.0401), lower levels of both WT1 and survivin co-expression (P = 0.0031), and the three-gene combination of lower WT1 + survivin + TERT (P = 0.0454) were powerful predictive factors for better EFS. As our findings were based on a single disease entity, that is, adult AML, they suggest that the expression of these genes may be critical for the immunobiology of AML to influence the clinical outcome in various ways.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, Seoul, Korea.
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Choi
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Sohn
authors.forename: So-Hye
authors.initials: SH
authors.lastname: Park
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Min
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001681:Biological Assay; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis; D000077022:Survivin; D019098:Telomerase / Q000235:genetics*; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D025721:WT1 Proteins; C583751:WT1 protein, human; C509186:TERT protein, human; D019098:Telomerase
keywords: AML; Wilms' tumor gene 1; leukemia-associated antigens; survivin; telomerase reverse transcriptase