Prognostic impact of RT-PCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia.
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.
Weisser
M
M
Laboratory for Leukemia Diagnostics, Medical Department III, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany. martin.weisser@med.uni-muenchen.de
Kern
W
W
Rauhut
S
S
Schoch
C
C
Hiddemann
W
W
Haferlach
T
T
Schnittger
S
S
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*
D012334:RNA, Neoplasm; D025721:WT1 Proteins