Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia
The prognostic impact of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML). Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. The clinical data of 870 pediatric patients with AML were downloaded...
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| Format: | Article |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.632094/full |
| _version_ | 1818958741314207744 |
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| author | Yin Wang Yin Wang Wen-Jun Weng Wen-Jun Weng Dun-Hua Zhou Dun-Hua Zhou Jian-Pei Fang Jian-Pei Fang Srishti Mishra Li Chai Lu-Hong Xu Lu-Hong Xu |
| author_facet | Yin Wang Yin Wang Wen-Jun Weng Wen-Jun Weng Dun-Hua Zhou Dun-Hua Zhou Jian-Pei Fang Jian-Pei Fang Srishti Mishra Li Chai Lu-Hong Xu Lu-Hong Xu |
| author_sort | Yin Wang |
| collection | DOAJ |
| description | The prognostic impact of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML). Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile, and prognosis of AML patients with WT1 mutations in this cohort. Our results showed that 6.7% of total patients harbored WT1 mutations. These WT1 mutations were closely associated with normal cytogenetics (P<0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P<0.001), and low complete remission induction rates (P<0.01). Compared to the patients without WT1 mutations, patients with WT1 mutations had a worse 5-year event-free survival (21.7 ± 5.5% vs 48.9 ± 1.8%, P<0.001) and a worse overall survival (41.4 ± 6.6% vs 64.3 ± 1.7%, P<0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation tended to improve the prognoses of WT1-mutated patients. Multivariate analysis demonstrated that WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). In conclusion, our findings have demonstrated that WT1 mutations are independent poor prognostic factors in pediatric AML. |
| first_indexed | 2024-12-20T11:30:34Z |
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| id | doaj.art-d33682aeaa454d0c8c5161b37fca7ddd |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T11:30:34Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-d33682aeaa454d0c8c5161b37fca7ddd2022-12-21T19:42:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.632094632094Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid LeukemiaYin Wang0Yin Wang1Wen-Jun Weng2Wen-Jun Weng3Dun-Hua Zhou4Dun-Hua Zhou5Jian-Pei Fang6Jian-Pei Fang7Srishti Mishra8Li Chai9Lu-Hong Xu10Lu-Hong Xu11Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaCancer Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Pathology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaThe prognostic impact of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML). Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile, and prognosis of AML patients with WT1 mutations in this cohort. Our results showed that 6.7% of total patients harbored WT1 mutations. These WT1 mutations were closely associated with normal cytogenetics (P<0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P<0.001), and low complete remission induction rates (P<0.01). Compared to the patients without WT1 mutations, patients with WT1 mutations had a worse 5-year event-free survival (21.7 ± 5.5% vs 48.9 ± 1.8%, P<0.001) and a worse overall survival (41.4 ± 6.6% vs 64.3 ± 1.7%, P<0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation tended to improve the prognoses of WT1-mutated patients. Multivariate analysis demonstrated that WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). In conclusion, our findings have demonstrated that WT1 mutations are independent poor prognostic factors in pediatric AML.https://www.frontiersin.org/articles/10.3389/fonc.2021.632094/fullacute myeloid leukemiaWT1 mutationspediatric patientsprognostic factorsFLT3/ITD mutations |
| spellingShingle | Yin Wang Yin Wang Wen-Jun Weng Wen-Jun Weng Dun-Hua Zhou Dun-Hua Zhou Jian-Pei Fang Jian-Pei Fang Srishti Mishra Li Chai Lu-Hong Xu Lu-Hong Xu Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia Frontiers in Oncology acute myeloid leukemia WT1 mutations pediatric patients prognostic factors FLT3/ITD mutations |
| title | Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia |
| title_full | Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia |
| title_fullStr | Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia |
| title_full_unstemmed | Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia |
| title_short | Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia |
| title_sort | wilms tumor 1 mutations are independent poor prognostic factors in pediatric acute myeloid leukemia |
| topic | acute myeloid leukemia WT1 mutations pediatric patients prognostic factors FLT3/ITD mutations |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.632094/full |
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