Kramarzova K, Boublikova L, Stary J, Trka J. Leukemia. 2013 Apr;27(5):1194–6. doi: 10.1038/leu.2012.291. Epub 2012 Oct 10. IF: 10,164
Department of Paediatric Haematology and Oncology
Abstract
Wilms' tumor gene 1 (WT1) is located on chromosome 11p13. As a zinc finger transcription factor, WT1 regulates expression of many target genes involved in regulation of cell cycle, proliferation, differentiation and apoptosis. Overexpression of WT1 was found in majority of acute leukemias and other hematological malignancies. WT1 has, therefore, been intensively studied as a potential prognostic factor, marker for minimal residual disease (MRD) and target for immunotherapy (summarized in references).
In this report, we focus on the role of WT1 as a marker for monitoring of malignant cells in patients with childhood acute myeloid leukemia (AML). Many important studies proved the usefulness of WT1 for this purpose, showing that this gene provides a promising tool for residual disease detection. In general, these studies were based on the analysis of bone marrow (BM) samples, while only minority used peripheral blood (PB) as a source of leukemic cells. Considering the fact, that the percentage of blasts can differ between BM and PB, one could assume that the choice of material for WT1 detection may influence the subsequent analysis. Nevertheless, no consensus has been made so far.
Comparison of paired BM and PB levels of WT1 revealed an excellent correlation between these values with the correlation coefficient of 0.89 (P<0.0001). However, there was no relation between WT1 levels in PB or BM and the percentage of blasts.
According to French-American-British (FAB) classification, M3 subtype of AML was associated with the highest WT1 expression, while patients with M5 AML had the lowest WT1 level (P<0.0001 for both BM and PB). Standard risk cases expressed WT1 on higher level compared with high risk group (P<0.0001 for both BM and PB). We could not prove any relation of WT1 level to age, sex or d15 treatment response. Neither did the expression of WT1 correlate with survival characteristics of our cohort of childhood AML; patients with high and low initial level of WT1 had the same relapse-free survival probability.
