Work

Romilostim for Trteatment of Children and Young Adults With Severe Aplastic Anemia and Myelodyplastic Syndrome: a Single Centre Pilot Study

Year: 2025

Type: article

Abstract: transplantation.This study compares clonal architecture and disease trajectory in idiopathic AA and HA-AA.Methods: All samples were evaluated using flow cytometry.HA-AA samples, including longitudinal ones, underwent T-cell receptor beta (TRB) sequencing (EuroClonality-NGS protocol) and whole exome sequencing (WES).In idiopathic AA patients with suspected germline predisposition, WES or panel sequencing was performed.Results: HA-AA is characterised by a predominance of activated (HLA-DR⁺) CD8⁺ T cells, unlike idiopathic AA, which typically lacks increased HLA-DR expression and CD8⁺ dominance, suggesting a distinct pathogenesis.No differences were found between RCC and AA histological subtypes.WES revealed no monogenic cause in HA-AA but detected variants of unknown significance, including CXCR4, ASXL1, WRAP53, and ACD.No variants of interest were detected in the AA group.TRB sequencing in HA-AA showed variable clonal expansion at diagnosis, with diversification following successful treatment in most-but not all -patients.Persistence of expanded clones did not necessarily portend poor response.CDR3 amino acid sequences were largely private, with occasional matches to viral antigen-associated sequences, such as CMV.Conclusions: HA-AA is associated with a distinct immunophenotypic and genotypic pattern irrespective of histology.HA-AA is marked by elevated activated CD8⁺ cells, detectable in peripheral blood during preceding hepatitis.TRB repertoire is restricted at the diagnosis of AA.Supported by NW25-05-00315 & GAUK 342525

Source: EJC Paediatric Oncology

DOI: 10.1016/j.ejcped.2025.100365

Authors: Anjali Sharathkumar, David Claassen, Sarah Bell

Institution: University of Iowa

Language: English

Topic: Blood disorders and treatments

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,340