Wilms tumour gene 1 overexpression in bone marrow as a marker for minimal residual disease in acute myeloid leukaemia.
OBJECTIVE
Wilms tumour gene 1 (WT1) is overexpressed in leucocytes of most acute myeloid leukaemia (AML) patients. However, the clinical relevance of WT1 gene expression as minimal residual disease (MRD) marker in AML has been questioned.


METHODS
We determined the expression of WT1 gene in bone marrow (BM) mononuclear cells of 100 AML patients at diagnosis and compared it with other MRD markers during follow up in 16 patients using quantitative reverse transcription-polymerase chain reaction.


RESULTS
The median WT1 gene expression was 9.7% of K562 cell line WT1 expression (lower quartile 1.5%, upper quartile 29.9%, n = 100) at diagnosis and, 0.053% (lower quartile 0.022%, upper quartile 0.125%, n = 87) in molecular or immunophenotypic remission. Median WT1 expression in control BM was 0.029% (lower quartile 0.013%, upper quartile 0.061%, n = 22). The upper 99% percentile of remission samples was 0.3%, which was regarded as the cut-off of increased WT1 gene expression in AML and was exceeded in 87% of all AML patients at diagnosis. WT1 and the other MRD markers showed only minor differences in profiles during follow-up. WT1 expression at diagnosis with median value 9.7% as the cut-off level or as a continuous variable had no prognostic significance for 2-yr survival.


CONCLUSIONS
The sensitivity of WT1 as a MRD marker was low due to the relatively high background WT1 gene expression in BM cells at remission and in subjects without haematological malignancies. Therefore, WT1 gene expression analysis would be beneficial only in those patients who do not have a more specific and sensitive MRD marker.
Hämäläinen
Mauri M
MM
Department of Clinical Chemistry, University of Turku, Turku, Finland. mauham@utu.fi
Kairisto
Veli
V
Juvonen
Vesa
V
Johansson
Janita
J
Aurén
Jukka
J
Kohonen
Kati
K
Remes
Kari
K
Salmi
Toivo T
TT
Helenius
Hans
H
Pelliniemi
Tarja-Terttu
TT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016162:Genes, Wilms Tumor; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D018709:Statistics, Nonparametric
D005819:Genetic Markers