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WT1 gene is overexpressed in myeloproliferative neoplasms, especially in myelofibrosis

Abstract : Classical Philadelphia-negative myeloproliferative neoplasms include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). They are characterized by the presence of driver mutations of JAK2, CALR or MPL genes. Overexpression of WT1 is used as a marker of minimal residual disease in acute myeloid leukemia, especially after allogeneic stem cell transplantation (SCT). We investigated WT1 expression at diagnosis in 152 MPN patients and showed that the WT1 transcript was overexpressed in PMFs and PVs compared to controls. In particular, WT1 transcript levels were higher in PMF than in ET and PV. WT1 transcript levels were significantly increased during myelofibrotic transformation of ET or PV. Using multi-variate linear regression, high WT1 transcript levels in PMF were associated with age over 65, splenomegaly and thrombocytopenia. The ROC curve analysis showed that a level of WT1 transcript > 10 WT1 copies/10 4 ABL1 enabled the diagnosis of PMF with a specificity of 95.8% (PMF vs ET; ROC AUC = 0.91). In myelofibrosis, studying follow-ups of WT1 transcript showed that this marker is of interest after allogeneic SCT. These results demonstrate that WT1 overexpression is a simple marker of myelofibrosis in MPN and could be used during patient follow-up.
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Submitted on : Thursday, January 24, 2019 - 2:12:09 PM
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Laurane Cottin, Jeremie Riou, Françoise Boyer, Anne Bouvier, Alain Zannetti, et al.. WT1 gene is overexpressed in myeloproliferative neoplasms, especially in myelofibrosis. Blood Cells, Molecules and Diseases, Elsevier, 2019, 75, pp.35-40. ⟨10.1016/j.bcmd.2018.12.004⟩. ⟨inserm-01992425⟩



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