Clonality analysis after retroviral-mediated gene transfer to CD34+ cells from the cord blood of ADA-deficient SCID neonates.
Nat Med
; 9(4): 463-8, 2003 Apr.
Article
em En
| MEDLINE
| ID: mdl-12640448
ABSTRACT
A clinical trial of retroviral-mediated transfer of the adenosine deaminase (ADA) gene into umbilical cord blood CD34(+) cells was started in 1993. ADA-containing peripheral blood mononuclear cells (PBMCs) have persisted in patients from this trial, with T lymphocytes showing the highest prevalence of gene marking. To gain a greater understanding of the nature and number of the transduced cells that were engrafted, we used linear amplification-mediated PCR (LAM-PCR) to identify clonal vector proviral integrants. In one patient, a single vector integrant was predominant in T lymphocytes at a stable level over most of the eight-year time span analyzed and was also detected in some myeloid samples. T-cell clones with the predominant integrant, isolated after eight years, showed multiple patterns of T-cell receptor (TCR) gene rearrangement, indicating that a single pre-thymic stem or progenitor cell served as the source of the majority of the gene-marked cells over an extended period of time. It is important to distinguish the stable pattern of monoclonal gene marking that we observed here from the progressive increase of a T-cell clone with monoclonal gene marking that results from leukemic transformation, as observed in two subjects in a clinical trial of gene therapy for X-linked severe combined immunodeficiency (SCID).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução Genética
/
Adenosina Desaminase
/
Imunodeficiência Combinada Severa
/
Técnicas de Transferência de Genes
/
Antígenos CD34
/
Sangue Fetal
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
/
Newborn
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article