Dongfen Du1,2, Lixia Zhu1, Yungui Wang3, Xiujin Ye1. 1. Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. 2. Shaoxing Central Blood Station, Shaoxing 312000, Zhejiang Province, China. 3. Department of Hematology and Institute of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Abstract
OBJECTIVE: To investigate the expression of Wilms'tumor 1 (WT1) gene in patients with acute myeloid leukemia (AML), and to explore its application in predicting prognosis of AML in patients with wild or mutated nucleophosmin 1(NPM1) and Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD). METHODS: One hundred and sixty-seven newly diagnosed AML patients(exclued M3 type) were enrolled in this study. The survival of patients were analyzed with Kaplan-Meier method. The clinical data, laboratory findings and the survival of patients were analyzed and compared between patients with high WT1 expression (high-WT1 group) and those with low WT1 expression (low-WT1 group), as well as among the patients with NPM1 or FLT3-ITD wild type and mutants. RESULTS: The overall response rates (ORR) in high-WT1 and low-WT1 groups were 65.9% (83/126) and 95.1% (39/41), respectively (P<0.01). Compared with the low-WT1 group, the high-WT1 group had lower 2-y overall survival (OS) rate (46.1% vs. 75.2%, P<0.05) and 2-y disease free survival (DFS) rate (43.5% vs. 68.5%, P<0.05). After induction chemotherapy, the patients with decreased WT1 gene expression ≥ 1log was associated with higher ORR and 2-y OS rate (all P<0.05), but the advantage of 2-y DFS rate was not shown (P>0.05). In patients with NPM1 wild type, the high-WT1 group had inferior ORR and 2-y OS rate (all P<0.05), while in the patients with FLT3-ITD wild type, the high-WT1 group had inferior ORR, 2-y OS rate and 2-y DFS rate (all P<0.05). In patients with NPM1 or FLT3 -ITD mutations, the WT1 expression had no significantly predicting values in treatment efficacy and survival (all P>0.05). CONCLUSIONS: WT1 gene overexpression indicated poor prognosis of AML patients; the patients with decreased WT1 gene expression ≥ 1 log after the first induction therapy show better prognosis than those with<1 log. The WT1 gene expression level at diagnosis can be used as an unfavorable prognostic factor for AML patients with NPM1 or FLT3-ITD wild types.
OBJECTIVE: To investigate the expression of Wilms'tumor 1 (WT1) gene in patients with acute myeloid leukemia (AML), and to explore its application in predicting prognosis of AML in patients with wild or mutated nucleophosmin 1(NPM1) and Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD). METHODS: One hundred and sixty-seven newly diagnosed AML patients(exclued M3 type) were enrolled in this study. The survival of patients were analyzed with Kaplan-Meier method. The clinical data, laboratory findings and the survival of patients were analyzed and compared between patients with high WT1 expression (high-WT1 group) and those with low WT1 expression (low-WT1 group), as well as among the patients with NPM1 or FLT3-ITD wild type and mutants. RESULTS: The overall response rates (ORR) in high-WT1 and low-WT1 groups were 65.9% (83/126) and 95.1% (39/41), respectively (P<0.01). Compared with the low-WT1 group, the high-WT1 group had lower 2-y overall survival (OS) rate (46.1% vs. 75.2%, P<0.05) and 2-y disease free survival (DFS) rate (43.5% vs. 68.5%, P<0.05). After induction chemotherapy, the patients with decreased WT1 gene expression ≥ 1log was associated with higher ORR and 2-y OS rate (all P<0.05), but the advantage of 2-y DFS rate was not shown (P>0.05). In patients with NPM1 wild type, the high-WT1 group had inferior ORR and 2-y OS rate (all P<0.05), while in the patients with FLT3-ITD wild type, the high-WT1 group had inferior ORR, 2-y OS rate and 2-y DFS rate (all P<0.05). In patients with NPM1 or FLT3 -ITD mutations, the WT1 expression had no significantly predicting values in treatment efficacy and survival (all P>0.05). CONCLUSIONS: WT1 gene overexpression indicated poor prognosis of AML patients; the patients with decreased WT1 gene expression ≥ 1 log after the first induction therapy show better prognosis than those with<1 log. The WT1 gene expression level at diagnosis can be used as an unfavorable prognostic factor for AML patients with NPM1 or FLT3-ITD wild types.