Evidence map›Paper›PMID 40399689›Full record

ArticleInternational journal of hematology2025

Whole-genome sequencing reveals genetic backgrounds in Japanese patients with hemophagocytic lymphohistiocytosis treated with the HLH-2004 protocol.

Ryu Yanagisawa, Manabu Wakamatsu, Dan Tomomasa, Kenichi Sakamoto, Rintaro Ono, Takehiko Doi, Ko Kudo, Hisanori Fujino, Kazuko Kudo, Akira Morimoto and 8 more

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Article in International journal of hematology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

18 authors.

Ryu YanagisawaDivision of Blood Transfusion, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. ryu@shinshu-u.ac.jp.ORCID http://orcid.org/0000-0003-4012-0958
Manabu WakamatsuDepartment of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Dan TomomasaDepartment of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Kenichi SakamotoDepartment of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Rintaro OnoDepartment of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
Takehiko DoiDepartment of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Ko KudoDepartment of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Hisanori FujinoDepartment of Pediatrics, Osaka Red Cross Hospital, Osaka, Japan.
Kazuko KudoDepartment of Pediatrics, Fujita Health University, Toyoake, Japan.
Akira MorimotoDepartment of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Japan.
Yoko ShiodaChildren's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
Takahiro YasumiDepartment of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hideki MakishimaDepartment of Hematology and Medical Oncology, Shinshu University School of Medicine, Nagano, Japan.
Hideki MuramatsuDepartment of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yoshiyuki TakahashiDepartment of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hirokazu KaneganeDepartment of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Yozo NakazawaDepartment of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
HLH/LCH Committee Members of the Japan Children’s Cancer Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition triggered by a combination of genetic predispositions and environmental factors. Reports of previous outcomes from the HLH-2004 protocol in Japan revealed patients with idiopathic HLH who had poor prognoses. This study aimed to reevaluate the genetic background of such patients to identify potential novel genetic variants.

methodsWhole-genome sequencing was performed on residual samples from HLH patients enrolled in a study of the HLH-2004 protocol in Japan, excluding those associated with Epstein-Barr virus infection. Sequence variants were interpreted based on the American College of Medical Genetics and Genomics standards and guidelines.

resultsNineteen patients were analyzed, including seven diagnosed with familial HLH (FHL) and twelve with unknown causes. Among patients with FHL, five had variants in PRF1 and two in UNC13D, consistent with the original diagnoses. Genetic variants (all UNC13D) were identified in three of the 12 previously undiagnosed patients. One patient had an unknown outcome and the others died of HLH.

conclusionFailure to establish a genetic diagnosis during initial evaluation may have negatively impacted the prognosis of patients with HLH. Comprehensive genetic studies and the development of early screening methods may improve treatment outcomes for HLH.

Indexed as

Lymphohistiocytosis, HemophagocyticWhole Genome SequencingAdolescentAdultChildChild, PreschoolEast Asian PeopleFemaleGenetic Predisposition to DiseaseHumansInfantJapanMaleMembrane ProteinsMiddle AgedPerforinMembrane ProteinsPerforinPRF1 protein, humanUNC13D protein, humanFHLGenetic variantHematopoietic cell transplantationHemophagocytosisPrimary HLH

Identifiers

PMID40399689

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