Identification of a novel CCDC22 mutation in a patient with severe Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis and aggressive natural killer cell leukemia
Abstract Aggressive natural killer cell leukemia (ANKL) is a rare neoplasm characterized by the systemic infiltration of Epstein–Barr virus (EBV)-associated NK cells, and rapidly progressive clinical course. We report the case of a 45-year-old man with intellectual disability who developed ANKL, and describe the identification of a novel genetic mutation of coiled-coil domain-containing 22 (CCDC22). He presented with persistent fever, severe pancytopenia, and hepatosplenomegary. Following bone marrow aspiration, numerous hemophagocytes were identified. High EBV viral load was detected in NK cells fractionation by qPCR. The initial diagnosis was EBV-related hemophagocytic lymphohistiocytosis (EBV–HLH). A combination of immunosuppressive drugs and chemotherapy was administered, but was unsuccessful in controlling the disease. Therefore, he was treated with HLA-matched related allogeneic hematopoietic stem cell transplantation. However, his condition deteriorated within 30 days, resulting in fatal outcome. Autopsy revealed many EBV-infected NK cells infiltrating major organs, consistent with ANKL. Furthermore, whole-exome sequencing identified a novel missense mutation of the CCDC22 gene (c.112G>A, p.V38M), responsible for X-linked intellectual disability (XLID). CCDC22 has been shown to play a role in NF-κB activation. Our case suggests that CCDC22 mutation might be implicated in pathogenesis of EBV–HLH and NK-cell neoplasms as well as XLID via possibly affecting NF-κB signaling..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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| Enthalten in: |
International journal of hematology - 109(2019), 6 vom: 31. Jan., Seite 744-750 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yamashita, Yusuke [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Aggressive natural killer cell leukemia |
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| Anmerkungen: |
© Japanese Society of Hematology 2019 |
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| doi: |
10.1007/s12185-019-02595-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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SPR025127659 |
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| 245 | 1 | 0 | |a Identification of a novel CCDC22 mutation in a patient with severe Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis and aggressive natural killer cell leukemia |
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| 520 | |a Abstract Aggressive natural killer cell leukemia (ANKL) is a rare neoplasm characterized by the systemic infiltration of Epstein–Barr virus (EBV)-associated NK cells, and rapidly progressive clinical course. We report the case of a 45-year-old man with intellectual disability who developed ANKL, and describe the identification of a novel genetic mutation of coiled-coil domain-containing 22 (CCDC22). He presented with persistent fever, severe pancytopenia, and hepatosplenomegary. Following bone marrow aspiration, numerous hemophagocytes were identified. High EBV viral load was detected in NK cells fractionation by qPCR. The initial diagnosis was EBV-related hemophagocytic lymphohistiocytosis (EBV–HLH). A combination of immunosuppressive drugs and chemotherapy was administered, but was unsuccessful in controlling the disease. Therefore, he was treated with HLA-matched related allogeneic hematopoietic stem cell transplantation. However, his condition deteriorated within 30 days, resulting in fatal outcome. Autopsy revealed many EBV-infected NK cells infiltrating major organs, consistent with ANKL. Furthermore, whole-exome sequencing identified a novel missense mutation of the CCDC22 gene (c.112G>A, p.V38M), responsible for X-linked intellectual disability (XLID). CCDC22 has been shown to play a role in NF-κB activation. Our case suggests that CCDC22 mutation might be implicated in pathogenesis of EBV–HLH and NK-cell neoplasms as well as XLID via possibly affecting NF-κB signaling. | ||
| 650 | 4 | |a Aggressive natural killer cell leukemia |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a EBV-related hemophagocytic lymphohistiocytosis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Allogeneic hematopoietic stem cell transplantation |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a CCDC22 |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Nishikawa, Akinori |4 aut | |
| 700 | 1 | |a Iwahashi, Yoshifumi |4 aut | |
| 700 | 1 | |a Fujimoto, Masakazu |4 aut | |
| 700 | 1 | |a Sasaki, Izumi |4 aut | |
| 700 | 1 | |a Mishima, Hiroyuki |4 aut | |
| 700 | 1 | |a Kinoshita, Akira |4 aut | |
| 700 | 1 | |a Hemmi, Hiroaki |4 aut | |
| 700 | 1 | |a Kanazawa, Nobuo |4 aut | |
| 700 | 1 | |a Ohshima, Kouichi |4 aut | |
| 700 | 1 | |a Imadome, Ken-Ichi |4 aut | |
| 700 | 1 | |a Murata, Shin-ichi |4 aut | |
| 700 | 1 | |a Yoshiura, Koh-ichiro |4 aut | |
| 700 | 1 | |a Kaisho, Tsuneyasu |4 aut | |
| 700 | 1 | |a Sonoki, Takashi |4 aut | |
| 700 | 1 | |a Tamura, Shinobu |4 aut | |
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