LEF1 EXPRESSION IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS: A MARKER FOR DIAGNOSIS AND SURVIVAL PREDICTION (LLC/LEF1 2024)

December 18, 2025 updated by: Elena Sabattini, IRCCS Azienda Ospedaliero-Universitaria di Bologna

RILEVANZA DIAGNOSTICA DELLA ESPRESSIONE DI LEF-1 NEL LINFOMA A PICCOLI LINFOCITI/LEUCEMIA LINFATICA CRONICA B

Chronic lymphocytic leukemia (CLL) is a highly heterogeneous B-cell hematological malignancy characterized by clonal expansion and accumulation of morphologically mature B-lymphocytes with a peculiar immunophenotype in peripheral blood, bone marrow, and secondary lymphoid tissues. Diagnosis is usually possible by flow cytometry, while lymph node and/or bone marrow biopsy may be helpful if immunophenotyping is inconclusive. A better understanding of pathogenesis has, recently, allowed the identification of new markers, improving patient stratification, implementing the therapeutic armamentarium with new agents targeting key intracellular signaling pathways. The canonical Wnt/β-catenin pathway is well recognized and known to drive malignant transformation of several cancer types including B-CLL. High expression of WNT3 and its transcription factor LEF1 in CLL considered as one of the strongest facts supporting the role of this pathway in CLL.

The evaluation of LEF-1 expression by immunohistochemistry in the diagnostic setting is still limited and a substantial number of CLL patients with negative LEF-1 expression has been reported. This is a study of LEF-1 expression to test the utility of using it for optimizing the B-CLL diagnosis and correlate it with the immunohistochemical, clinical and molecular data and compare LEF-1 negative and positive cases to identify a possible LEF-1 expression related signature that could be useful in differential diagnosis, in prognostic stratification and possibility of using targeted drugs

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) is the most common chronic leukemia in adults in Western countries. SLL/CLL is classified as a chronic lymphoproliferative disorder within the category of mature B-cell neoplasms according to the World Health Organization (WHO) classification, and is characterized by the relentless accumulation of mature B lymphocytes displaying a distinctive immunophenotype. The disease may involve peripheral blood, bone marrow, lymph nodes, and the spleen. The median age at diagnosis is approximately 70 years, although about 10% of cases occur in young adults, and males are affected more frequently than females. In Western countries, the incidence is 2-6 cases per 100,000 inhabitants per year, increasing with age.¹ The clinical course of CLL is highly heterogeneous: most patients have an indolent course requiring no therapy or delayed treatment with prolonged survival, whereas others present with an aggressive disease requiring early treatment and experiencing frequent relapses.

SLL/CLL is generally diagnosed during routine blood testing in asymptomatic patients who exhibit absolute lymphocytosis, often with Gumprecht shadows visible on peripheral blood smears (representing fragile lymphocytes disrupted during slide preparation). The diagnosis of SLL/CLL is based on the presence of ≥5,000/µl clonal B lymphocytes in peripheral blood, which on flow cytometry are CD19+, CD5+, CD23+, CD200+, with dim CD20 expression, weak CD22 and/or CD79b, and weak surface immunoglobulin expression with light-chain restriction. Diagnosis is usually achievable through immunophenotyping of peripheral blood, whereas lymph node biopsy and/or bone marrow biopsy may be useful when immunophenotyping is inconclusive.

In the diagnostic work-up of SLL/CLL, CD5, CD19, CD20, CD23, and surface or cytoplasmic kappa/lambda light chains are considered essential markers, while CD10, CD43, CD79b, CD81, CD200, and ROR1 serve as additional antigens useful for differential diagnosis among small B-cell lymphomas/leukemias. Beyond assessing del(11q), del(13q), del(17p), and trisomy 12, TP53 mutational analysis and evaluation of somatic hypermutation (SHM) of the immunoglobulin heavy-chain variable region (IGHV) are essential for comprehensive prognostic assessment in SLL/CLL. IGHV mutational status and TP53 status are included in the CLL International Prognostic Index (CLL-IPI), together with age, clinical stage, and β2-microglobulin levels. Assessment of karyotypic complexity and the mutational status of BTK, PLCG2, and BCL2 remain desirable additional investigations within a targeted-therapy approach.

In recent years, improved understanding of SLL/CLL pathogenesis has clarified preneoplastic conditions (e.g., monoclonal B-cell lymphocytosis), enabled identification of novel diagnostic, prognostic, and predictive markers, refined patient stratification, and expanded the therapeutic armamentarium with new agents targeting key intracellular signaling pathways. Among these, several studies have demonstrated dysregulation of the WNT/β-catenin pathway in SLL/CLL. The final mediator of this pathway is LEF-1 (lymphoid enhancer-binding factor 1), a key transcription factor regulating cell proliferation and survival and playing a fundamental role in lymphopoiesis. LEF-1 is normally expressed in a subset of T cells and in B-cell precursors but is silenced in mature B cells; however, gene expression profiling studies have shown overexpression of LEF-1 in SLL/CLL compared with normal B cells. This expression is detectable by immunohistochemistry in tissue samples, where its presence has been confirmed. Nonetheless, although LEF-1 expression has demonstrated usefulness in distinguishing SLL/CLL from other indolent B-cell lymphomas, its diagnostic application remains limited. Moreover, a subset of CLL patients does not express LEF-1, and the characteristics of these patients have not yet been investigated.

The aim of this study, with an anticipated enrollment of up to 350 patients with a confirmed diagnosis of SLL/CLL and available molecular data at diagnosis, is to re-evaluate immunohistochemical expression on biopsy specimens (most commonly bone-marrow biopsies) to:

  1. confirm actual LEF-1 expression positivity, and
  2. statistically assess potential clinical correlations between LEF-1-positive and LEF-1-negative subsets, in an effort to identify possible diagnostic, prognostic, or therapeutic implications.

The study is observational, multicenter, national, retrospective/ Prospective cohort.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
350

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
    • BOLOGNA
      • Bologna, BOLOGNA, Italy, 40138

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients diagnosed with SLL/CLL who turned to the Hemolymphatic Pathology Unit of the IRCCS - Bologna University Hospital, Policlinico S. Orsola-Malpighi, and the Hemolymphatic Pathology Unit of the Pathological Anatomy Unit, Policlinico Universitario Umberto I, Rome, from January 2014 to December 2024.

Description

Inclusion Criteria:

  • Patients with a confirmed diagnosis of SLL/CLL - B
  • Males and females, adults at diagnosis
  • Patients with available tissue (lymph node, extralymph node, or bone marrow) on which immunohistochemical analysis including LEF-1 has been performed and who have already submitted mutational and/or cytogenetic analysis data.

Exclusion Criteria:

  • - Patients with LEF1-positive indolent B-cell lymphomas not supported by a genetic evaluation with SSL/CLL.
  • CLL cases for which a biopsy is not available

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
LEF1 expression
Time Frame: From the beginning of the study to the analysis of all the results: 24 months
To evaluate the expression of the LEF-1 molecule at diagnosis, in a cohort of patients with a clinical and histopathological diagnosis of SLL/CLL, with an expected value of around 70% of positive cases.
From the beginning of the study to the analysis of all the results: 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Relationship
Time Frame: From the beginning of the study to the analysis of all the results: 24 months
To evaluate the relationship between immunohistochemical and mutational parameters collected at diagnosis and clinical data.
From the beginning of the study to the analysis of all the results: 24 months
New markers
Time Frame: From the beginning of the study to the analysis of all the results: 24 months
Identify new possible diagnostic, prognostic or therapeutic markers.
From the beginning of the study to the analysis of all the results: 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

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Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 31, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 18, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2025

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 2, 2026

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LLC/LEF1 2024

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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