Six-gene Signature Predicts Survival in Mantle Cell Lymphoma Patients, Study Reports

Six-gene Signature Predicts Survival in Mantle Cell Lymphoma Patients, Study Reports
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A six-gene signature related to B-cell activity can predict survival in patients with mantle cell lymphoma (MCL), a study suggests.

Conducted by researchers in Italy, the study, “A B-Cell Receptor-Related Gene Signature Predicts Survival In Mantle Cell Lymphoma: Results From The “Fondazione Italiana Linfomi” MCL-0208 Trial,” appeared in the journal Haematologica.

MCL is a type of B-cell non-Hodgkin’s lymphoma with a diverse clinical course and prognosis. Due to this variability, diagnostic tools are needed that are able to differentiate patients into risk classes so that appropriate treatment strategies can be defined.

Besides tools such as an MCL clinical prognostic score and the Ki-67 proliferation index, both of which classify patients into groups with different overall survival rates, the use of positron emission tomography (PET) scans enables the monitoring of post-treatment response in MCL patients. Approaches based on gene expression analysis to predict overall survival also showed validity in these patients.

Recent research indicates that the B-cell receptor (BCR) pathway — important to healthy immune function — may be associated with MCL and other types of B-cell malignancies.

Based on this, researchers in this study examined if the levels of six genes, mostly from the BCR pathway, could predict the survival of advanced MCL patients who had been treated in the FIL-MCL-0208 Phase 3 clinical trial (NCT02354313).

This trial compared Revlimid (lenalidomide) maintenance therapy with observation in patients with MCL who went into complete or partial remission following first-line treatment with chemotherapy and stem cell transplantation.

The six genes selected for building the survival model were AKT3, BCL2, BTK, CD79B, PIK3CD, and SYK.

The analysis included 83 patients with advanced stage MCL, who were younger than 66 years — a median age of 56 years.

Assessment of the transcriptome — the collection of all messenger RNA molecules, which is generated from DNA in gene expression — of peripheral blood samples led to the identification of two subgroups with a different expression of genes from the BCR pathway, called the B-cell receptor-low and B-cell receptor-high groups.

Subsequent analysis showed that the B-cell receptor-high subgroup correlated with shorter progression-free survival (PFS), defined as the length of time during and after treatment with no cancer progression. Patients in this subgroup also showed elevated levels of lactate dehydrogenase, an enzyme involved in energy production in cells.

Researchers then combined the BCR groups with predictions through the Ki-67 index, which showed that PFS was shortest (20.5 months) for patients who were both BCR-high and Ki-67-high. Findings were validated in an independent MCL group treated with different schedules.

“In conclusion, this 6-gene signature associates with a poor clinical response,” the scientists wrote. “Our data underscore the increasing importance of BCR-related genes in the pathogenesis and development of MCL.”

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