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

NCT ID: NCT05934045

Last Updated: 2023-07-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2025-12-31

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.

Conditions

ALK-Positive Anaplastic Large Cell Lymphoma

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: RETROSPECTIVE

Study Groups

ALCL patient samples (serum)

serum collected at diagnosis, during treatment and/or at relapse

RNAseq

Intervention Type: BIOLOGICAL

there is no intervention done.

Interventions

RNAseq

there is no intervention done.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laurence Lamant

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

IUCT-Oncopole University Hospital

Toulouse, , France

Countries

France

Other Identifiers

French Ministry of Health

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

RC31/22/0507

Identifier Type: -

Identifier Source: org_study_id