A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.
Nat Commun
; 15(1): 3662, 2024 Apr 30.
Article
em En
| MEDLINE
| ID: mdl-38688902
ABSTRACT
Hematopoietic stem cell gene therapy (GT) using a γ-retroviral vector (γ-RV) is an effective treatment for Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency. Here, we describe a case of GT-related T-cell acute lymphoblastic leukemia (T-ALL) that developed 4.7 years after treatment. The patient underwent chemotherapy and haploidentical transplantation and is currently in remission. Blast cells contain a single vector insertion activating the LIM-only protein 2 (LMO2) proto-oncogene, confirmed by physical interaction, and low Adenosine Deaminase (ADA) activity resulting from methylation of viral promoter. The insertion is detected years before T-ALL in multiple lineages, suggesting that further hits occurred in a thymic progenitor. Blast cells contain known and novel somatic mutations as well as germline mutations which may have contributed to transformation. Before T-ALL onset, the insertion profile is similar to those of other ADA-deficient patients. The limited incidence of vector-related adverse events in ADA-deficiency compared to other γ-RV GT trials could be explained by differences in transgenes, background disease and patient's specific factors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
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Adenosina Desaminase
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Imunodeficiência Combinada Severa
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Transplante de Células-Tronco Hematopoéticas
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Agamaglobulinemia
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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Vetores Genéticos
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Proto-Oncogene Mas
Limite:
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
/
Nature communications
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Itália