BCL6-rearrangements Implications in Non-Hodgkin Lymphomas. (BCL6-RINHL)

Civil Hospices of Lyon

Status: Active, not recruiting

Conditions: Marginal Zone Lymphoma; Follicular Lymphoma; Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma

Treatments: Genetic: Molecular analysis; Other: Histopathological analysis

Study type: Observational

Funder types: Other

Identifiers

NCT06424379

69HCL24_0515

Details and patient eligibility

About

Non-Hodgkin lymphomas (NHLs) constitute a heterogeneous group of malignant neoplasms, with diverse clinical behaviors and distinct pathologic and molecular characteristics. Among these lymphomas, follicular lymphomas (FLs), marginal zone lymphomas (MZLs) and diffuse large B-cell lymphomas (DLBCLs) emerge as the most prevalent entities. While FL and MZL are representative of indolent B-cell lymphomas, characterized by a slow progression of the disease and favorable clinical outcomes, DLBCL stands out as an aggressive lymphoma, often occuring from the transformation of a pre-existing indolent lymphoma.

Chromosome translocations are a hallmark of some NHL subtypes, offering insights into their molecular pathogenesis. For instance, the conventional FL is genetically characterized by the t(14;18) chromosomal translocation, found in 85-90% of cases, resulting in sustained elevation of the antiapoptotic protein B-cell lymphoma 2 (BCL2). However, certain FL cases lack BCL2 translocations and exhibit distinct clinical, morphological and phenotypical features with genetic heterogeneity.

A subset of BCL2-negative FLs displays rearrangements within chromosomal region 3q27, inducing abnormal modulation of B-cell lymphoma 6 (BCL6) expression. The BCL6 gene plays a critical role in germinal center development and B-cell differentiation. Previous investigations indicate that BCL6 rearrangements (BCL6-R) manifest distinct pathological and genetic features, diverging from classical FL presentations.

FLs carrying BCL6-R commonly share a specific CD10- Bcl-2- Bcl-6+ phenotype, often accompanied by a monocytoid component and increased frequency of diffuse architectural patterns. Patients with BCL6-R tend to exhibit advanced clinical stages and complex genetic profiles.

MZLs present differential diagnostic challenges due to shared monocytoid components, phenotypes traits, and common genetic features. The similarities observed between BCL6-R FL and MZL suggest a convergence in both morphological and genetic aspects, leading to intricate differentiation. Traditionally, these indolent NHLs with BCL6-R were categorized as FL and incorporated into the FL category in the WHO classification. However, few studies highlight the occurrence of BCL6-R in MZLs. This observation gives rise to the hypothesis that indolent NHLs exhibiting BCL6-R might correspond to a continuum comprising both FL and MZL.

Additionally, BCL6-R has been frequently documented in DLBCL cases with residual MZL component. These DLBCL cases might display a mutational profile reminiscent of MZL. This suggests a plausible origin of BCL6-R DLBCL from indolent BCL6-R MZLs or BCL6-R FLs cases.

Enrollment: 135 estimated patients

Sex: All

Ages: 25 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnostic of non-Hodgkin's lymphoma at anatomy and cytology department of Lyon Sud hospital
• Rearrangement of the BCL6 gene detected by FISH analysis
• Diagnostic of the disease between january 2016 and december 2023

Exclusion criteria

• Patients diagnosed with primary cutaneous centrofollicular B lymphoma, composite lymphoma, anaplastic B lymphoma or primary B lymphoma of the mediastinum.
• Presence of a rearrangement of the BLC2 gene or the CMYC gene in FISH
• Presence of a non-significant BCL6 gene rearrangement (<5% of rearranged cells)

Trial design

135 participants in 3 patient groups

Follicular lymphomas with BCL6 gene rearrangement

Description:

Diagnoses of follicular lymphomas based on the last World Health Organization (WHO) classification of haematolymphoid tumours at the time of occurrence of the disease. Fluorescence in situ hybridization (FISH) utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.

Treatment:

Other: Histopathological analysis

Genetic: Molecular analysis

Marginal zone lymphomas with BCL6 gene rearrangement

Description:

Diagnoses of marginal zone lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.

Treatment:

Other: Histopathological analysis

Genetic: Molecular analysis

Diffuse large B-cells lymphomas with BCL6 gene rearrangement

Description:

Diagnoses of diffuse large B-cells lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.

Treatment:

Other: Histopathological analysis

Genetic: Molecular analysis