Myeloid Sarcoma Type of Acute Promyelocytic Leukemia With a Cryptic Insertion of RARA Into FIP1L1: The Clinical Utility of NGS and Bioinformatic Analyses
BackgroundAcute promyelocytic leukemia (APL) is characterized by the presence of coagulopathy at onset and translocation t (15; 17) (q22; 21), meanwhile, other translocation variants of APL have also been reported. The FIP1L1–RARA fusion gene has recently been reported as a novel RARA-associated fus...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.688203/full |
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| author | Yongren Wang Yongren Wang Yaoyao Rui Yaoyao Rui Ying Shen Jian Li Jian Li Poning Liu Poning Liu Qin Lu Qin Lu Yongjun Fang Yongjun Fang |
| author_facet | Yongren Wang Yongren Wang Yaoyao Rui Yaoyao Rui Ying Shen Jian Li Jian Li Poning Liu Poning Liu Qin Lu Qin Lu Yongjun Fang Yongjun Fang |
| author_sort | Yongren Wang |
| collection | DOAJ |
| description | BackgroundAcute promyelocytic leukemia (APL) is characterized by the presence of coagulopathy at onset and translocation t (15; 17) (q22; 21), meanwhile, other translocation variants of APL have also been reported. The FIP1L1–RARA fusion gene has recently been reported as a novel RARA-associated fusion gene.ObjectivesWe report a case of de novo myeloid sarcoma (MS) type of APL with FIP1L1–RARA found by next-generation sequencing (NGS) that was not detected by conventional analyze analysis for RARA translocations.MethodsWe performed typical morphological, magnetic resonance imaging (MRI), conventional tests for PML–RARA dual-fusion translocation probe, high-through sequencing and NGS. Meanwhile, bioinformatics analyses were done by using public repositories, including ONCOMINE, COSMIC, and GeneMANIA analysis.ResultsA 28-month-old girl with a complex karyotype that includes 46,XX,t(4;17)(q12;q22)[9]/46,idem,del(16)(q22)[3]/45,idem,-x,-4,-9,-15,del(16)(q22),+marl,+mar2,+mar3[7]/46,xx[3], c.38G>A (p.Gly13Asp) in the KRAS gene, and a cryptic insertion of RARA gene into the FIP1L1 gene was diagnosed with APL complicated by the de novo MS.ConclusionWe report a FIP1L1–RARA fusion in a child with APL who presented with an extramedullary tumor in the skull without the classic karyotype using NGS, whom we treated with good results. NGS analysis should be considered for APL variant cases. Further experimental studies to the association between the mutation in KRAS gene and FIP1L1–RARA fusion on the clinical phenotype and progression of APL are needed to identify more effective therapeutic targets for APL. |
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| format | Article |
| id | doaj.art-4f0cd12eaf254b90a9e615f758a01c8b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-18T01:44:12Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-4f0cd12eaf254b90a9e615f758a01c8b2022-12-21T21:25:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-06-011110.3389/fonc.2021.688203688203Myeloid Sarcoma Type of Acute Promyelocytic Leukemia With a Cryptic Insertion of RARA Into FIP1L1: The Clinical Utility of NGS and Bioinformatic AnalysesYongren Wang0Yongren Wang1Yaoyao Rui2Yaoyao Rui3Ying Shen4Jian Li5Jian Li6Poning Liu7Poning Liu8Qin Lu9Qin Lu10Yongjun Fang11Yongjun Fang12Department of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Nanjing Medical University, Nanjing, ChinaDepartment of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Nanjing Medical University, Nanjing, ChinaDepartment of Gastroenterology, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Nanjing Medical University, Nanjing, ChinaDepartment of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Nanjing Medical University, Nanjing, ChinaDepartment of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Nanjing Medical University, Nanjing, ChinaDepartment of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, ChinaKey Laboratory of Hematology, Nanjing Medical University, Nanjing, ChinaBackgroundAcute promyelocytic leukemia (APL) is characterized by the presence of coagulopathy at onset and translocation t (15; 17) (q22; 21), meanwhile, other translocation variants of APL have also been reported. The FIP1L1–RARA fusion gene has recently been reported as a novel RARA-associated fusion gene.ObjectivesWe report a case of de novo myeloid sarcoma (MS) type of APL with FIP1L1–RARA found by next-generation sequencing (NGS) that was not detected by conventional analyze analysis for RARA translocations.MethodsWe performed typical morphological, magnetic resonance imaging (MRI), conventional tests for PML–RARA dual-fusion translocation probe, high-through sequencing and NGS. Meanwhile, bioinformatics analyses were done by using public repositories, including ONCOMINE, COSMIC, and GeneMANIA analysis.ResultsA 28-month-old girl with a complex karyotype that includes 46,XX,t(4;17)(q12;q22)[9]/46,idem,del(16)(q22)[3]/45,idem,-x,-4,-9,-15,del(16)(q22),+marl,+mar2,+mar3[7]/46,xx[3], c.38G>A (p.Gly13Asp) in the KRAS gene, and a cryptic insertion of RARA gene into the FIP1L1 gene was diagnosed with APL complicated by the de novo MS.ConclusionWe report a FIP1L1–RARA fusion in a child with APL who presented with an extramedullary tumor in the skull without the classic karyotype using NGS, whom we treated with good results. NGS analysis should be considered for APL variant cases. Further experimental studies to the association between the mutation in KRAS gene and FIP1L1–RARA fusion on the clinical phenotype and progression of APL are needed to identify more effective therapeutic targets for APL.https://www.frontiersin.org/articles/10.3389/fonc.2021.688203/fullacute promyelocytic leukemiamyeloid sarcomaFIP1L1–RARA fusionnext-generation sequencingKRAS genebioinformatic analyses |
| spellingShingle | Yongren Wang Yongren Wang Yaoyao Rui Yaoyao Rui Ying Shen Jian Li Jian Li Poning Liu Poning Liu Qin Lu Qin Lu Yongjun Fang Yongjun Fang Myeloid Sarcoma Type of Acute Promyelocytic Leukemia With a Cryptic Insertion of RARA Into FIP1L1: The Clinical Utility of NGS and Bioinformatic Analyses Frontiers in Oncology acute promyelocytic leukemia myeloid sarcoma FIP1L1–RARA fusion next-generation sequencing KRAS gene bioinformatic analyses |
| title | Myeloid Sarcoma Type of Acute Promyelocytic Leukemia With a Cryptic Insertion of RARA Into FIP1L1: The Clinical Utility of NGS and Bioinformatic Analyses |
| title_full | Myeloid Sarcoma Type of Acute Promyelocytic Leukemia With a Cryptic Insertion of RARA Into FIP1L1: The Clinical Utility of NGS and Bioinformatic Analyses |
| title_fullStr | Myeloid Sarcoma Type of Acute Promyelocytic Leukemia With a Cryptic Insertion of RARA Into FIP1L1: The Clinical Utility of NGS and Bioinformatic Analyses |
| title_full_unstemmed | Myeloid Sarcoma Type of Acute Promyelocytic Leukemia With a Cryptic Insertion of RARA Into FIP1L1: The Clinical Utility of NGS and Bioinformatic Analyses |
| title_short | Myeloid Sarcoma Type of Acute Promyelocytic Leukemia With a Cryptic Insertion of RARA Into FIP1L1: The Clinical Utility of NGS and Bioinformatic Analyses |
| title_sort | myeloid sarcoma type of acute promyelocytic leukemia with a cryptic insertion of rara into fip1l1 the clinical utility of ngs and bioinformatic analyses |
| topic | acute promyelocytic leukemia myeloid sarcoma FIP1L1–RARA fusion next-generation sequencing KRAS gene bioinformatic analyses |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.688203/full |
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