Study
Comprehensive Genomic Characterization of Gene Therapy-Induced T-cell Acute Lymphoblastic Leukemia (H007)
Study ID | Alternative Stable ID | Type |
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EGAS00001003870 | Other |
Study Description
Six out of ten patients in a hematopoietic stem cell gene therapy (GT) trial for Wiskott-Aldrich syndrome (WAS) developed T-cell acute lymphoblastic leukemia (T-ALL) associated with gamma-retroviral vector integration at the LMO2 locus. We hypothesized that detailed molecular analysis of T-ALL driven by temporally defined first deregulation of LMO2 might offer valuable insights into the pathogenesis of GT-associated and sporadic T-ALL (HIPO project 007). In all six patients whole-genome and transcriptome sequencing demonstrated that in addition to oncogenic chromosomal translocations involving the T-cell receptor loci, retrovirally induced leukemias faithfully recapitulated secondary genomic events observed in sporadic T-ALL. Multiple genetic events culminated in the development of a rapidly proliferating leukemic clone and onset of clinical manifestation at 1.3 to 5 years after infusion of the gene corrected transplant. These genetic alterations affected NOTCH1 and PI3K signaling, cell cycle regulation as wells as T-cell transcription factors LEF1 and TCF1. Two of the six cases ... (Show More)
Study Datasets 1 dataset.
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Dataset ID | Description | Technology | Samples |
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EGAD00001006016 |
NA
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HiSeq X Ten,Illumina HiSeq 2000 | 12 |
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