Deciphering the Role of Circular RNAs in ALKpositive Anaplastic Large-cell Lymphoma

Active, not recruiting

• Conditions: ALK-Positive Anaplastic Large Cell Lymphoma
• Interventions: Biological: RNAseq

• Registration Number: NCT05934045
• Lead Sponsor: University Hospital, Toulouse

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.

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 Timeline

• Study Start: 2023-01-01
• Primary Completion: 2023-06-01
• Study First Submitted: 2023-06-23
• Status Verified: 2023-07
• Study First Submitted QC: 2023-07-03
• Last Update Submitted: 2023-07-03
• Study First Posted: 2023-07-06
• Last Update Posted: 2023-07-06
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• patient at diagnosis of ALK+ ALCL
• patient at the time of relapse for ALK+ ALCL
• patient without ALK+ ALCL

Exclusion Criteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
ALCL patient samples (serum)	RNAseq	serum collected at diagnosis, during treatment and/or at relapse

Primary Outcome Measures

Name	Time	Method
Number of participants with relapse and circulating circRNA	1 year after the end of treatment	RNAseq analysis

Trial Locations

Locations (1)

IUCT-Oncopole University Hospital; 🇫🇷 Toulouse, France