scTALLmap · Single-cell map of the composition and evolution of T-cell acute lymphoblastic leukemia
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-03-31
- EU contribution
- €178,320
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Single-cell map of the composition and evolution of T-cell acute lymphoblastic leukemia
Spaniards have their daily siesta, Germans like sausages and Belgians love beer. Stereotypes can certainly be misleading, just like judging a cell by its membership to a particular cell type. For instance, we now know that tumors are tremendously heterogeneous and, in the era of single-cell sequencing, we have the exquisite opportunity to judge each individual cell with unprecedented resolution. This ability to profile single cells can specially advance our understanding of blood malignancies, a perfect model for single-cell studies since blood cells are already in suspension. In particular, we have investigated acute lymphoblastic leukemia (ALL), a frequent type of cancer in children in which the bone marrow produces too many lymphocytes (a type of white blood cell). ALL is a success story in pediatric oncology, since the prognosis (chance of recovery) for children suffering from ALL has remarkably improved over the last decades and is now > 90%. However, these children undergo a very intense 2-year treatment, based on a combination of high-dose chemotherapy drugs, and they suffer from long-term side-effects. Still, approximately 10% of the cases do not respond to the treatment and have high chances of relapse (disease recurrence) with a fatal outcome. This blood cancer shows extensive intratumoral heterogeneity, meaning that is composed by a mixture of clones (or leukemia subpopulations) with different mutation combinations. This heterogeneity might be the underlying reason for an incomplete response to treatment and for the development of relapse. To facilitate the clinical implementation of better risk classification methods accounting for patient’s heterogeneity, it is essential to: 1) generate a reference single-cell map for leukemia and 2) accumulate evidence on how the leukemia composition at the time of diagnosis affects the response to treatment. With this aim, in this European MSCA funded project, we have built a comprehensive single-cell overview of the composition, development and response to therapy for the childhood T-cell (T-ALL) aggressive subtype.
Data: CORDIS, © European Union
Project objective
Spaniards have their daily siesta, Germans like sausages and Belgians love beer. Stereotypes can certainly be misleading, just like judging a cell by its membership to a particular cell type, the so-called population-based analysis. Nowadays we know that tumors are tremendously heterogeneous and, in the era of single-cell sequencing, we have the exquisite opportunity to study each individual cell with unprecedented resolution. Acute lymphoblastic leukemia (ALL), which is the most common cancer in children, shows extensive genetic intratumoral heterogeneity. This heterogeneity might be the underlying reason for an incomplete response to treatment and for the development of relapse. In order to envision its clinical implementation, it is essential to first i) generate a single-cell map and ii) accumulate evidence on how the subclonal composition affects the response to treatment. With this aim, I will build a comprehensive single-cell overview of the composition, development and response to therapy for the aggressive subtype T-cell ALL. I will perform integrative single-cell genome and transcriptome profiling of ex vivo carefully selected pediatric samples at diagnosis, during drug treatment and in case of relapse. This approach will provide realtime temporal information about the sensitivity of each cell type to the therapy and about how relapse can develop. I will use state-of-the-art single-cell technologies to which the host institute has early access. Moreover, I will apply my previous single-cell expertise and bring a unique mix of experimental and computational skills to the lab. The results of scTALLmap, will have significant impact in leukemia by paving the way for improved risk-stratification based on the cellular heterogeneity and the presence of high-risk subclones at diagnosis. Ultimately, it will permit the design of novel and more personalized therapeutic modalities sparing toxicity and targeting the full complement of leukemia subclones.
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
Data: CORDIS, © European Union