title: Prognostic impact of RT-PCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia.
abstract: In search for general PCR targets for minimal residual disease (MRD) studies in acute myeloid leukemia (AML), Wilms' tumor gene 1 (WT1) expression was assessed by real-time RT-PCR relative to the control gene ABL in 569 archived samples of AML patients (pts). Pts were analyzed at diagnosis (n=116) and during follow-up (n=105, median 4 times, range 2--17). Median follow-up time was 258 days (range 16--1578 days). In 66 pts, the WT1 expression was analyzed in comparison to a second PCR marker or to multiparameter flow cytometry. Quantitative WT1 levels correlated to the clinical course or a second marker in 83-96% of the cases. Prognostic significance of WT1 levels was analyzed at diagnosis and three intervals: (1) days 16--60, (2) days 61--120, and (3) days 121--180 after start of chemotherapy. Higher levels of WT1 expression were associated with shorter overall survival (OS) and event-free survival (EFS) within intervals 2 and 3 but not at diagnosis or interval 1. In addition, within these intervals, WT1/ABL levels <or=0.4% were associated with improved OS and EFS. An increase of WT1 levels was detected in 16/44 cases, which subsequently relapsed within a median of 38 days (range 8--180 days). In conclusion, quantification of WT1 may be used for MRD studies and for prognostification in AML.
authors.affiliation: Laboratory for Leukemia Diagnostics, Medical Department III, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany. martin.weisser@med.uni-muenchen.de
authors.forename: M
authors.initials: M
authors.lastname: Weisser
authors.forename: W
authors.initials: W
authors.lastname: Kern
authors.forename: S
authors.initials: S
authors.lastname: Rauhut
authors.forename: C
authors.initials: C
authors.lastname: Schoch
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
authors.forename: T
authors.initials: T
authors.lastname: Haferlach
authors.forename: S
authors.initials: S
authors.lastname: Schnittger
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D012334:RNA, Neoplasm / Q000032:analysis*; D012008:Recurrence; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013997:Time Factors; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D012334:RNA, Neoplasm; D025721:WT1 Proteins