The Wilms' tumor gene is frequently expressed in acute myeloblastic leukemias and may provide a marker for residual blast cells detectable by PCR.
BACKGROUND
The tumor suppressor gene wt-1 was isolated by cytogenetic deletion analysis of patients with Wilms' tumor (wt-1). This gene encodes for a zinc finger DNA-binding protein with transcription-repressing properties. During normal ontogenesis it is expressed in a time- and tissue-dependent manner mainly in the kidneys and gonads. Recently, the expression of wt-1 in acute leukemias (AL) was reported. Here we investigated the prognostic potential of wt-1 mRNA expression during the course of the disease using the PCR technique.


METHODS
Blast cells from 83 patients with newly diagnosed AML and 20 AML patients during follow-up in complete remission were analyzed for wt-1 mRNA expression. Peripheral blood mononuclear cells (PBMNC) and bone marrow (BM) from healthy persons (n = 13) and sorted CD34-positive cells from normal donors (n = 4) were used as negative controls.


RESULTS
Wt-1-specific m-RNA was detectable in 67/83 (81%) patients with AML. Normal donors did not express wt-1 m-RNA but in 1/4 sorted CD34+ cell samples a weak amplified product was observed. After achieving cytological CR 14/20 studied patients lost wt-1 expression. In 7/8 patients in morphological CR the reappearance of wt-1 expression preceded relapse of the disease, in 1/8 patients wt-1 remained positive in CR. Response to therapy, disease-free survival, overall survival and FAB-subtype did not correlate with wt-1 m-RNA expression in newly diagnosed AML before therapy.


CONCLUSIONS
In the majority of acute leukemias wt-1 is expressed and probably blast cell-associated, at least in levels detectable by PCR. Wt-1 mRNA was detectable in bone marrow cells of AML patients in clinical CR. The results strongly suggest that the persistence or reappearance of wt-1 predicts relapse of the disease prior to morphological relapse.
Brieger
J
J
Medical Clinic III, Hematology-Oncology, J. W. Goethe University, Frankfurt/M., Germany.
Weidmann
E
E
Maurer
U
U
Hoelzer
D
D
Mitrou
P S
PS
Bergmann
L
L
D000328:Adult; D000368:Aged; D001483:Base Sequence; D015870:Gene Expression / Q000502:physiology*; D016162:Genes, Wilms Tumor / Q000502:physiology*; D005819:Genetic Markers; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism
D005819:Genetic Markers; D012333:RNA, Messenger