Ying Yang1, Chanjuan Wang2, Dong Wang1, Lei Cui2, Na Li2, Hongyun Lian1, Honghao Ma1, Yunze Zhao1, Liping Zhang1, Wei Liu3, Yizhuo Wang4, Wanshui Wu5, Rui Zhang6, Zhigang Li7, Tianyou Wang8. 1. Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56, Nanlishi Road, Xicheng district, Beijing, 100045, China. 2. Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56, Nanlishi Road, Xicheng district, Beijing, 10045, China. 3. Department of Hematology Oncology, Children's Hospital Affiliated To Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, China. 4. Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100176, China. 5. Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. 6. Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56, Nanlishi Road, Xicheng district, Beijing, 100045, China. ruizh1973@126.com. 7. Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56, Nanlishi Road, Xicheng district, Beijing, 10045, China. ericlzg70@hotmail.com. 8. Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56, Nanlishi Road, Xicheng district, Beijing, 100045, China. wangtianyou@bch.com.cn.
Abstract
PURPOSE: To analyze the genetic and clinical features of children with MAP2K1-mutated Langerhans cell histiocytosis (LCH). METHODS: We compared the clinical features of 37 children with MAP2K1-mutated LCH with those of the BRAFV600E mutation group (n = 133) and no known mutation group (n = 59) in the same period. RESULTS: We found 13 mutations of the MAP2K1 gene, which were mainly concentrated at p.53-62 and p.98-103. The most common mutation site was c.172_186del (12/37). Compared with the BRAFV600E mutation group, the patients with MAP2K1 mutations were mainly characterized by single-system multiple bone involvement (P = 0.022), with later disease onset (P = 0.029) as well as less involvement of risk organs, especially liver (P = 0.024). There was no significant difference in clinical features compared with the no known mutation group. The 2-year progression-free survival rate of first-line treatment (ChiCTR1900025783, 07/09/2019) in MAP2K1-mutated patients was 65.6% ± 9.5%. The prognosis of patients with lung involvement was poor [HR (95% CI) = 6.312 (1.769-22.526), P = 0.005]. More progression or relapses could be found in patients with bony thorax involvement (8/17 vs. 2/20, P = 0.023), yet involvements in other sites of bones, such as craniofacial bone involvement (8/26 vs. 2/11, P = 0.688) and limb bone involvement (5/12 vs. 5/25, P = 0.240), were not correlated to disease progression or relapse. CONCLUSION: The children with MAP2K1-mutated LCH have specific clinical features requiring clinical stratification and precise treatment. MAP2K1-mutated patients with lung involvement (especially with bony thorax involvement) had poor prognosis.
PURPOSE: To analyze the genetic and clinical features of children with MAP2K1-mutated Langerhans cell histiocytosis (LCH). METHODS: We compared the clinical features of 37 children with MAP2K1-mutated LCH with those of the BRAFV600E mutation group (n = 133) and no known mutation group (n = 59) in the same period. RESULTS: We found 13 mutations of the MAP2K1 gene, which were mainly concentrated at p.53-62 and p.98-103. The most common mutation site was c.172_186del (12/37). Compared with the BRAFV600E mutation group, the patients with MAP2K1 mutations were mainly characterized by single-system multiple bone involvement (P = 0.022), with later disease onset (P = 0.029) as well as less involvement of risk organs, especially liver (P = 0.024). There was no significant difference in clinical features compared with the no known mutation group. The 2-year progression-free survival rate of first-line treatment (ChiCTR1900025783, 07/09/2019) in MAP2K1-mutated patients was 65.6% ± 9.5%. The prognosis of patients with lung involvement was poor [HR (95% CI) = 6.312 (1.769-22.526), P = 0.005]. More progression or relapses could be found in patients with bony thorax involvement (8/17 vs. 2/20, P = 0.023), yet involvements in other sites of bones, such as craniofacial bone involvement (8/26 vs. 2/11, P = 0.688) and limb bone involvement (5/12 vs. 5/25, P = 0.240), were not correlated to disease progression or relapse. CONCLUSION: The children with MAP2K1-mutated LCH have specific clinical features requiring clinical stratification and precise treatment. MAP2K1-mutated patients with lung involvement (especially with bony thorax involvement) had poor prognosis.
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