CIRComa: Deciphering the Role of Circular RNAs in ALKpositive Anaplastic Large-cell Lymphoma
Study Details
Study Description
Brief Summary
The objective of thE project is to determine, whether circRNAs could be used as circulating prognostic and/or predictive biomarkers of ALK+ ALCL resistance to treatment and whether they can be exploited as therapeutic targets.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Anaplastic large-cell lymphoma (ALCL) is an aggressive T-cell pediatric lymphoma. 85% of ALK+ ALCL cases harbor a fusion between the nucleophosmin (NPM) and anaplastic lymphoma kinase (ALK) genes, leading to a constitutively activated and oncogenic fusion protein. Most ALK+ ALCL cases initially respond well to the frontline chemotherapy, but 30% of patients relapse and are of poor prognosis. Understanding the origins of therapy resistance is of major importance to improve treatment and patient prognosis. Current research highlights deregulated expression of regulatory non-coding RNAs (ncRNAs) as an important factor in therapy resistance. To date, microRNAs and long noncoding RNAs have been linked to therapy resistance in ALK+ ALCL. Circular RNAs (circRNAs) are a class of highly stable noncoding RNAs that have recently come into the focus of researchers. circRNAs can control target gene expression by e.g. interacting with microRNAs or proteins. This project aims to elucidate their role in ALK+ ALCL biology including their impact on noncoding RNA networks and therapy resistance. This project will (1) identify a signature of circRNAs associated with therapy resistance in ALK+ ALCL, (2) analyze their effect on treatment response, (3) elucidate their mechanism of action, and (4) evaluate circRNA candidates as predictive and prognostic plasma biomarkers using liquid biopsies. The goal of the study is to characterize the role of candidate circRNAs in this well-defined cancer type, which can serve as a model for other ALK+ cancers. Project results will add to the current mechanistic understanding of ALK+ ALCL pathogenesis and the origins of therapy resistance, and could define new druggable targets and associated predictive biomarkers for high-risk disease. Establishing the blood-based alternative confirmation for the ALK+ ALCL diagnosis could also produce a less invasive predictive tool capable of longitudinal patient monitoring for early relapse detection.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| ALCL patient samples (serum) serum collected at diagnosis, during treatment and/or at relapse |
Biological: RNAseq
there is no intervention done.
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Outcome Measures
Primary Outcome Measures
- Number of participants with relapse and circulating circRNA [1 year after the end of treatment]
RNAseq analysis
Eligibility Criteria
Criteria
Inclusion Criteria:
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patient at diagnosis of ALK+ ALCL
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patient at the time of relapse for ALK+ ALCL
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patient without ALK+ ALCL
Exclusion Criteria:
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | IUCT-Oncopole University Hospital | Toulouse | France | 31500 |
Sponsors and Collaborators
- University Hospital, Toulouse
- Institut National de la Santé Et de la Recherche Médicale, France
Investigators
- Principal Investigator: Laurence Lamant, University Hospital, Toulouse
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RC31/22/0507
- French Ministry of Health