GATA2 mutations and overexpression in pediatric acute myeloid leukemia
Background: GATA2 is important for the regulation of development and proliferation of early pluripotent hematopoietic precursors, and precise GATA2 expression is critical in myeloid lineage maturation. GATA2 mutations have been reported in acute myeloid leukemia (AML) but only few studies of GATA2 m...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-08-01
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| Series: | Pediatric Hematology Oncology Journal |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468124519302463 |
| _version_ | 1828343499394646016 |
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| author | Zhenzhen Yang Xingjuan Wang Xi Chen Hu Dou Yi Huang Ling Lu Lin Zou Junqin Bi Meng Su Jie Yu Liming Bao |
| author_facet | Zhenzhen Yang Xingjuan Wang Xi Chen Hu Dou Yi Huang Ling Lu Lin Zou Junqin Bi Meng Su Jie Yu Liming Bao |
| author_sort | Zhenzhen Yang |
| collection | DOAJ |
| description | Background: GATA2 is important for the regulation of development and proliferation of early pluripotent hematopoietic precursors, and precise GATA2 expression is critical in myeloid lineage maturation. GATA2 mutations have been reported in acute myeloid leukemia (AML) but only few studies of GATA2 mutations and overexpression in pediatric AML have been reported so far and none was in Chinese populations. Method: We analyzed GATA mutation status and expression state in a cohort of 309 Chinese children with AML. We also assessed the impact of GATA2 mutations and overexpression on outcomes in our pediatric AML cohort. Results: GATA2 mutations were observed in 2.6% of the patients and they were clustered in the ZF1 and ZF2 domains. GATA2 overexpression was detected in 72.7% of the cases, with the highest and lowest expression levels observed in adverse subgroup and favorable subgroup, respectively. In the entire cohort, shorter overall survival (OS) and event-free survival (EFS) showed a stronger correlation with GATA2 overexpression than with normal GATA2 levels (OS: p = 0.021; EFS: p = 0.018). Such an inverse relationship between GATA2 overexpression and survivals was evident among AML patients with normal cytogenetics (OS: p = 0.037; EFS: p = 0.024) and adverse features (OS: p = 0.021; EFS: p = 0.023), but not observed in favorable subgroup (OS: p = 0.323; EFS: p = 0.342), suggesting that the negative influence of GATA2 overexpression on pediatric AML outcomes is risk subgroup specific. Conclusion: Our results demonstrate that GATA2 mutations in pediatric AML are rare, and are primarily clustered in the zinc finger (ZF) domains. Our results suggest that GATA2 overexpression exerts a negative influence on survivals, and the effect is risk subgroup specific in pediatric childhood AML. Keywords: Acute myeloid leukemia, Pediatric, GATA2, Overexpression, Outcome |
| first_indexed | 2024-04-13T23:43:10Z |
| format | Article |
| id | doaj.art-14401e263290408e96f9a934bee87062 |
| institution | Directory Open Access Journal |
| issn | 2468-1245 |
| language | English |
| last_indexed | 2024-04-13T23:43:10Z |
| publishDate | 2019-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pediatric Hematology Oncology Journal |
| spelling | doaj.art-14401e263290408e96f9a934bee870622022-12-22T02:24:25ZengElsevierPediatric Hematology Oncology Journal2468-12452019-08-01425663GATA2 mutations and overexpression in pediatric acute myeloid leukemiaZhenzhen Yang0Xingjuan Wang1Xi Chen2Hu Dou3Yi Huang4Ling Lu5Lin Zou6Junqin Bi7Meng Su8Jie Yu9Liming Bao10Center for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, ChinaCenter for Reproductive Medicine of Baoji Maternal and Child Health Hospital, Shanxi, ChinaCenter for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, Key Laboratory of Pediatrics in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, ChinaDepartment of Rheumatology, Huashan Hospital, Fudan University, Shanghai, ChinaCenter for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, ChinaCenter for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Pathology, University of Colorado School of Medicine, Aurora, CO, USADepartment of Hematology and Oncology, Children's Hospital of Chongqing Medical University, Chongqing, China; Corresponding author. Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University, No.136 Zhongshang 2nd Road, Chongqing, 400014, China.Center for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA; Corresponding author. Department of Pathology, University of Colorado School of Medicine, 12705 E. Montview Boulevard, Suite 400, Aurora, CO, 80045, USA.Background: GATA2 is important for the regulation of development and proliferation of early pluripotent hematopoietic precursors, and precise GATA2 expression is critical in myeloid lineage maturation. GATA2 mutations have been reported in acute myeloid leukemia (AML) but only few studies of GATA2 mutations and overexpression in pediatric AML have been reported so far and none was in Chinese populations. Method: We analyzed GATA mutation status and expression state in a cohort of 309 Chinese children with AML. We also assessed the impact of GATA2 mutations and overexpression on outcomes in our pediatric AML cohort. Results: GATA2 mutations were observed in 2.6% of the patients and they were clustered in the ZF1 and ZF2 domains. GATA2 overexpression was detected in 72.7% of the cases, with the highest and lowest expression levels observed in adverse subgroup and favorable subgroup, respectively. In the entire cohort, shorter overall survival (OS) and event-free survival (EFS) showed a stronger correlation with GATA2 overexpression than with normal GATA2 levels (OS: p = 0.021; EFS: p = 0.018). Such an inverse relationship between GATA2 overexpression and survivals was evident among AML patients with normal cytogenetics (OS: p = 0.037; EFS: p = 0.024) and adverse features (OS: p = 0.021; EFS: p = 0.023), but not observed in favorable subgroup (OS: p = 0.323; EFS: p = 0.342), suggesting that the negative influence of GATA2 overexpression on pediatric AML outcomes is risk subgroup specific. Conclusion: Our results demonstrate that GATA2 mutations in pediatric AML are rare, and are primarily clustered in the zinc finger (ZF) domains. Our results suggest that GATA2 overexpression exerts a negative influence on survivals, and the effect is risk subgroup specific in pediatric childhood AML. Keywords: Acute myeloid leukemia, Pediatric, GATA2, Overexpression, Outcomehttp://www.sciencedirect.com/science/article/pii/S2468124519302463 |
| spellingShingle | Zhenzhen Yang Xingjuan Wang Xi Chen Hu Dou Yi Huang Ling Lu Lin Zou Junqin Bi Meng Su Jie Yu Liming Bao GATA2 mutations and overexpression in pediatric acute myeloid leukemia Pediatric Hematology Oncology Journal |
| title | GATA2 mutations and overexpression in pediatric acute myeloid leukemia |
| title_full | GATA2 mutations and overexpression in pediatric acute myeloid leukemia |
| title_fullStr | GATA2 mutations and overexpression in pediatric acute myeloid leukemia |
| title_full_unstemmed | GATA2 mutations and overexpression in pediatric acute myeloid leukemia |
| title_short | GATA2 mutations and overexpression in pediatric acute myeloid leukemia |
| title_sort | gata2 mutations and overexpression in pediatric acute myeloid leukemia |
| url | http://www.sciencedirect.com/science/article/pii/S2468124519302463 |
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