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Molecular classification and outcomes in pediatric aplastic anemia with myeloid neoplasm-associated gene variants
Danni Li1, Meiling Liao1, Yuye Liu1
1Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
Insights
Genetic variations in pediatric aplastic anemia (AA) are linked to clonal hematopoiesis. This study found that while gene variants like TET2, ASXL1, and MPL are common, survival depends on disease severity and early hematological response, not genotype.
Area of Science:
- Hematology
- Genetics
- Oncology
Background:
- Limited research exists on clonal hematopoiesis in pediatric aplastic anemia (AA).
- Genetic variations are increasingly recognized as significant in AA pathogenesis.
- Understanding these variants is crucial for classifying disease and predicting outcomes in children.
Purpose of the Study:
- To investigate the molecular classification of pediatric AA.
- To identify common gene variants associated with myeloid neoplasms in children with AA.
- To analyze the correlation between these gene variants and patient outcomes.
Main Methods:
- Retrospective analysis of clinical features, gene variants, and their mechanisms.
- Identification of gene variants in 46 pediatric AA patients.
- Correlation analysis between genotypes, treatment efficacy, and survival.
Main Results:
- Twenty gene variants were identified in 46 pediatric AA patients, with TET2, ASXL1, and MPL being most frequent.
- Mutated genes primarily affected epigenetic and signal transduction pathways (39.1%).
- Immunosuppressive therapy efficacy did not differ significantly across gene variant groups. Survival was linked to disease severity and early hematological response (3 months), not genotype.
Conclusions:
- TET2, ASXL1, and MPL variants are common in pediatric AA and involve epigenetic and signaling pathways.
- Immunosuppressive therapy (IST) effectiveness is not significantly influenced by specific gene variants.
- Disease severity and achieving a hematological response early are key determinants of survival in pediatric AA patients with myeloid neoplasm-associated gene variants.
Background:
The genetic variations in aplastic anemia (AA) patients are closely related to clonal hematopoiesis, but there is limited research on this topic in children with AA. The aim of this study is to investigate the molecular classification and outcomes of children with AA combined with myeloid neoplasm-associated gene variants.
Methods:
The clinical features, types of gene variants, mechanisms of action of the mutated genes, and correlations between gene variants and the outcomes of AA patients with myeloid neoplasm-associated gene variants were retrospectively analyzed.
Results:
Forty-six AA patients with myeloid neoplasm-associated gene variants were included, and a total of 20 gene variants were identified. The most frequent variant affected TET2 (9 patients, 19.6%), followed by ASXL1 (5 patients, 10.9%) and MPL (5 patients, 10.9%). Other variants, in descending order, affected TERT (4 patients); SH2B3, FLT3, ETV6, and JAK2 (3 patients each); BCOR, BCORL1, TP53, KIT, and SF3B1 (2 patients each); and CALR, GATA2, RUNX1, CBL, IDH1, IDH2, and WT1 (1 patient each). Six patients had 2 gene variants. The original mechanisms of action of the mutated genes mainly involved epigenetics and signal transduction pathways; both groups of genes were affected in 39.1% (18/46) of the patients. The difference in the efficacy of immunosuppressive therapy (IST) among the different gene groups was not significant. Disease severity (P = 0.046) and hematological response at 3 months (P = 0.002), 6 months (P = 0.001), 9 months (P = 0.001), and 1 year (P = 0.001) were important factors affecting survival time, but genotype was not. None of the patients experienced clonal evolution by the end of the follow-up cut-off time.
Conclusion:
In patients with AA combined with myeloid tumor neoplasm-associated gene variants, TET2, ASXL1 and MPL variants were the most frequently observed and primarily involved epigenetics and signal transduction pathways. There was no significant difference in the efficacy of IST among patients with different gene variants. Survival time was associated with disease severity, and the development of a hematological response-particularly when achieved at 3 months-was an independent key factor, whereas genotype was not.
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