Perforin Gene Mutations in Patients with Acquired Aplastic Anemia

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2007 Feb 22

PMID 17311987

Citations 27

Authors

Elena E Solomou

Federica Gibellini

Brian Stewart

Daniela Malide

Maria Berg

Valeria Visconte

Spencer Green

Richard Childs

Stephen J Chanock

Neal S Young

Affiliations

Soon will be listed here.

Abstract

Perforin is a cytolytic protein expressed mainly in activated cytotoxic lymphocytes and natural killer cells. Inherited perforin mutations account for 20% to 40% of familial hemophagocytic lymphohistiocytosis, a fatal disease of early childhood characterized by the absence of functional perforin. Aplastic anemia, the paradigm of immune-mediated bone marrow failure syndromes, is characterized by hematopoietic stem cell destruction by activated T cells and Th1 cytokines. We examined whether mutations in the perforin gene occurred in acquired aplastic anemia. Three nonsynonymous PRF1 mutations among 5 unrelated patients were observed. Four of 5 patients with the mutations showed some hemophagocytosis in the bone marrow at diagnosis. Perforin protein levels in these patients were very low or absent, and perforin granules were completely absent. Natural killer (NK) cell cytotoxicity from these patients was significantly decreased. Our data suggest that PRF1 genetic alterations help explain the aberrant proliferation and activation of cytotoxic T cells and may represent genetic risk factors for bone marrow failure.

Citing Articles

Genetics of Primary Hemophagocytic Lymphohistiocytosis.

Karageorgos S, Platt A, Bassiri H Adv Exp Med Biol. 2024; 1448:75-101.

PMID: 39117809 DOI: 10.1007/978-3-031-59815-9_7.

Germline variants in acquired aplastic anemia: current knowledge and future perspectives.

Wang P, Jiang W, Lai T, Liu Q, Shen Y, Ye B Haematologica. 2024; 109(9):2778-2789.

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Hemophagocytic Lymphohistiocytosis Gene Variants in Severe Aplastic Anemia and Their Impact on Hematopoietic Cell Transplantation Outcomes.

Rafati M, McReynolds L, Wang Y, Hicks B, Jones K, Spellman S Transplant Cell Ther. 2024; 30(8):770.e1-770.e10.

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New-onset aplastic anemia after SARS-CoV-2 vaccination.

Chatzikalil E, Kattamis A, Diamantopoulos P, Solomou E Int J Hematol. 2023; 118(6):667-681.

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The hyperinflammatory spectrum: from defects in cytotoxicity to cytokine control.

Planas R, Felber M, Vavassori S, Pachlopnik Schmid J Front Immunol. 2023; 14:1163316.

PMID: 37187762 PMC: 10175623. DOI: 10.3389/fimmu.2023.1163316.

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