Article

High expression of WT1 gene in acute myeloid leukemias with more predominant WT1+17AA isoforms at relapse.

Department of Hematology, The First People's Hospital of Changzhou, Third Affiliated to Suzhou University, Changzhou, China.
Leukemia research (Impact Factor: 2.36). 05/2009; 34(1):46-9. DOI: 10.1016/j.leukres.2009.04.004
Source: PubMed

ABSTRACT Real-time quantitative reverse transcriptase polymerase chain reaction method was established for detecting the expression levels of WT1 gene and WT1+17AA isoforms in 226 acute myeloid leukemia (AML) bone marrow (BM) cells. The results showed that WT1 gene was 2-3 logarithms expressed more in AML BM cells at initial diagnosis or relapse than in normal BM cells (p<0.001), with predominant WT1+17AA isoforms expression (the ratio of WT1+17AA/WT1 more than 0.50). Interestingly the ratio of WT1+17AA/WT1 was statistically higher in relapsed AMLs than in initially diagnosed (p=0.01), speculating that WT1+17AA isoforms might participate in AML relapse.

0 Bookmarks
 · 
76 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Early stage detection of cancer is the key to provide a better outcome for therapeutic intervention. Most routine screening tools for cancer detection are largely based on examination of cell morphology, tissue histology and measurement of serum markers, which lack sufficient sensitivity and/or specificity for early detection of cancer. Indeed, most secreted proteins studied as cancer screening biomarkers have low sensitivity and/or low specificity and this could be due to the use of non-sensitive techniques or due the fact that several of these tumor markers are also produced by normal tissues. Altogether, these facts pinpoint to the urgent need for the discovery of innovative tools and novel tumour markers for cancer screening, diagnosis, and prognosis. Recently, scientists and clinicians have shifted to innovative techniques in order to identify and characterize biomarkers that drive the development and progression of cancer, and to discover upstream genes/proteins which could be useful to detect early-stage cancer, predict prognosis, determine therapy efficacy, or to be novel drug targets. This chapter contains three sections that will discuss different but complementary innovative techniques that are being developed for the detection of early biomarkers in cancers. The first technique will focus on the use of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) for the quantitation of the Wilms' tumor gene (WT1) mRNA (WT1 Assay). The WT1 mRNA is a relatively new marker of several types of leukemia and myelodysplastic syndrome (MDS). This WT1 assay makes it possible to rapidly assess the effectiveness of treatment and to evaluate the degree of eradication of leukemic cells as well as the continuous assessment of the MDS progression and its evolution to overt acute myeloid leukemia. The second section will highlight the use of Mass Spectrometry (MS) technique as an important analytical tool in clinical proteomics, primarily in the disease-specific discovery, identification and characterization of proteomic biomarkers and patterns. MS-based proteomics is increasingly being used in clinical validation and diagnostic method development. In this section, we will describe the current state of MS in clinical proteomics applied to early detection of cancer biomarkers with a focus on ovarian and breast cancers including both biomarker discovery and clinical diagnosis. In the last section we will focus on the Surface Plasmon Resonance (SPR) technique which is primarily used to detect bimolecular interaction and has recently gained enormous interest and popularity for its versatility and high sensitivity especially when it is coupled to MS.
    Cancer Biomarkers: Non-Invasive Early Diagnosis and Prognosis, Edited by Debmalya Barh, Angelo Carpi, Mukesh Verma, and Mehmet Gunduz, 10/2013: chapter 4: pages 900; Taylor & Francis/CRC Press., ISBN: 9781466584280
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the mechanism of action of leukemic oncogene Wilms' tumor gene 1 (WT1) remains unclear, WT1 has already been used in monitoring of patients with acute myeloid leukemia (AML) and it is being tested for immunotherapy. More detailed understanding of the role of WT1 in leukemia may improve its utilization. At least 36 isoforms may be produced. Four major variants denoted as -5/-KTS, -5/+KTS, +5/-KTS and +5/+KTS are produced by combining splicing of exon 5 and KTS sequence. In this study, we report applicability of newly developed real-time RT PCRs enabling for the first time full quantification of the four major WT1 splicing variants. Following careful optimization and testing of quantification reliability of four assays, we analyzed 34 samples of patients with AML and 12 samples of patients with chronic myeloid leukemia (CML) at the time of diagnosis. Analyses of five more CML patients provided insight into WT1 variants expression kinetics. We found predominance of +5/+KTS in both diagnoses. Comparison of WT1 variant expression in AML and CML patients' groups differing in response to therapy suggested possible importance of particular WT1 variant levels as markers of further disease course.
    Blood Cells Molecules and Diseases 05/2012; 49(1):41-7. · 2.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: WT1 plays a dual role in leukemia development, probably due to an imbalance in the expression of the 4 main WT1 isoforms. We quantify their expression and evaluate them in a series of AML patients. Our data showed a predominant expression of isoform D in AML, although in a lower quantity than in normal CD34+ cells. We found a positive correlation between the total WT1 expression and A, B and C isoforms. The overexpression of WT1 in AML might be due to a relative increase in A, B and C isoforms, together with a relative decrease in isoform D expression.
    Leukemia research 10/2013; · 2.36 Impact Factor