Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutations
TTMV::RARA is a recently reported fusion gene associated with acute promyelocytic leukemia (APL), caused by the integration of torque teno mini virus (TTMV) genomic fragments into the second intron of the RARA gene. Currently, there have been only six documented cases, with clinical presentations sh...
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Elsevier
2024-03-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024031384 |
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| author | Linya Wang Jiaqi Chen Bei Hou Ying Wu Jun Yang Xiaosu Zhou Qihui Chen Xue Chen Yang Zhang Fang Wang Jiancheng Fang Panxiang Cao Mingyue Liu Yanan Li Pan Zhang Yan Liu Ruidong Zhang Hongxing Liu Huyong Zheng |
| author_facet | Linya Wang Jiaqi Chen Bei Hou Ying Wu Jun Yang Xiaosu Zhou Qihui Chen Xue Chen Yang Zhang Fang Wang Jiancheng Fang Panxiang Cao Mingyue Liu Yanan Li Pan Zhang Yan Liu Ruidong Zhang Hongxing Liu Huyong Zheng |
| author_sort | Linya Wang |
| collection | DOAJ |
| description | TTMV::RARA is a recently reported fusion gene associated with acute promyelocytic leukemia (APL), caused by the integration of torque teno mini virus (TTMV) genomic fragments into the second intron of the RARA gene. Currently, there have been only six documented cases, with clinical presentations showing significant variability. Although initial responses to all-trans retinoic acid (ATRA) treatment may be observed in patients with TTMV::RARA-APL, the overall prognosis remains unfavorable among infrequent reported cases. This article presents a pediatric case that manifested as PML::RARA-negative APL with central nervous system involvement at onset. The patient experienced both intramedullary and extramedullary relapse one year after undergoing allogeneic hematopoietic stem cell transplantation. Upon identification as TTMV::RARA-APL and subsequent administration of two rounds of ATRA-based treatment, the patient rapidly developed multiple RARA ligand-binding domain mutations and demonstrated extensive resistance to ATRA and various other therapeutic interventions. Additionally, the patient experienced ARID1A mutant clone expansion and progressed MYC-targeted gene activation. This case represents the first documentation of extramedullary involvement at both the initial diagnosis and relapse stages, emphasizing the intricate clinical features and challenges associated with the rapid accumulation of multiple ATRA-resistant mutations in TTMV::RARA-APL, characterizing it as a distinct and complex sub-entity of atypical APL. |
| first_indexed | 2024-03-07T21:28:19Z |
| format | Article |
| id | doaj.art-f8a750839ecd4d93b256ae35947ea551 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T23:15:42Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-f8a750839ecd4d93b256ae35947ea5512024-03-17T07:57:21ZengElsevierHeliyon2405-84402024-03-01105e27107Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutationsLinya Wang0Jiaqi Chen1Bei Hou2Ying Wu3Jun Yang4Xiaosu Zhou5Qihui Chen6Xue Chen7Yang Zhang8Fang Wang9Jiancheng Fang10Panxiang Cao11Mingyue Liu12Yanan Li13Pan Zhang14Yan Liu15Ruidong Zhang16Hongxing Liu17Huyong Zheng18Hematology 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, ChinaMolecular Medicine Center, Beijing Lu Daopei Institute of Hematology, Beijing, China; Department of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, ChinaHematology 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, ChinaHematology 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, ChinaStem Cell Transplantation Department, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Hematology, 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, ChinaMolecular Medicine Center, Beijing Lu Daopei Institute of Hematology, Beijing, ChinaPrecision Medicine Center, Beijing Gene Profile Research Institute, Beijing, ChinaDepartment of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, ChinaMolecular Medicine Center, Beijing Lu Daopei Institute of Hematology, Beijing, China; Department of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, ChinaDepartment of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, ChinaDepartment of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, ChinaMolecular Medicine Center, Beijing Lu Daopei Institute of Hematology, Beijing, China; Department of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, ChinaDepartment of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, ChinaHematology and Oncology Department, Beijing Children's Hospital Baoding Hospital, Baoding, ChinaStem Cell Transplantation Department, Beijing Children's Hospital, Baoding Hospital, Capital Medical University, Baoding, ChinaHematology and Oncology Department, Beijing Children's Hospital Baoding Hospital, Baoding, ChinaHematology 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, ChinaMolecular Medicine Center, Beijing Lu Daopei Institute of Hematology, Beijing, China; Department of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, China; Division of Pathology & Laboratory Medicine, Beijing Lu Daopei Hospital, Beijing, China; Department of Oncology, Capital Medical University, Beijing, China; Corresponding author. Molecular Medicine Center, Beijing Lu Daopei Institute of Hematology; Department of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital; Division of Pathology & Laboratory Medicine, Beijing Lu Daopei Hospital; Department of Oncology, Capital Medical University, 100176, ChinaHematology 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, China; Corresponding author. 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, 100045, China.TTMV::RARA is a recently reported fusion gene associated with acute promyelocytic leukemia (APL), caused by the integration of torque teno mini virus (TTMV) genomic fragments into the second intron of the RARA gene. Currently, there have been only six documented cases, with clinical presentations showing significant variability. Although initial responses to all-trans retinoic acid (ATRA) treatment may be observed in patients with TTMV::RARA-APL, the overall prognosis remains unfavorable among infrequent reported cases. This article presents a pediatric case that manifested as PML::RARA-negative APL with central nervous system involvement at onset. The patient experienced both intramedullary and extramedullary relapse one year after undergoing allogeneic hematopoietic stem cell transplantation. Upon identification as TTMV::RARA-APL and subsequent administration of two rounds of ATRA-based treatment, the patient rapidly developed multiple RARA ligand-binding domain mutations and demonstrated extensive resistance to ATRA and various other therapeutic interventions. Additionally, the patient experienced ARID1A mutant clone expansion and progressed MYC-targeted gene activation. This case represents the first documentation of extramedullary involvement at both the initial diagnosis and relapse stages, emphasizing the intricate clinical features and challenges associated with the rapid accumulation of multiple ATRA-resistant mutations in TTMV::RARA-APL, characterizing it as a distinct and complex sub-entity of atypical APL.http://www.sciencedirect.com/science/article/pii/S2405844024031384Acute promyelocytic leukemia (APL)Torque teno mini virus (TTMV)Whole transcriptome sequencing (WTS)TTMV::RARACase report |
| spellingShingle | Linya Wang Jiaqi Chen Bei Hou Ying Wu Jun Yang Xiaosu Zhou Qihui Chen Xue Chen Yang Zhang Fang Wang Jiancheng Fang Panxiang Cao Mingyue Liu Yanan Li Pan Zhang Yan Liu Ruidong Zhang Hongxing Liu Huyong Zheng Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutations Heliyon Acute promyelocytic leukemia (APL) Torque teno mini virus (TTMV) Whole transcriptome sequencing (WTS) TTMV::RARA Case report |
| title | Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutations |
| title_full | Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutations |
| title_fullStr | Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutations |
| title_full_unstemmed | Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutations |
| title_short | Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutations |
| title_sort | case report of pediatric ttmv related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of rara lbd mutations |
| topic | Acute promyelocytic leukemia (APL) Torque teno mini virus (TTMV) Whole transcriptome sequencing (WTS) TTMV::RARA Case report |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024031384 |
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