Randall S. Davis, M.D. University of Alabama at Birmingham

THERAPY/ PROGNOSTIC

Potential Role of FCRL2 as a Surrogate Marker of IgVH Mutation in CLL

Grant awarded in 2008

Abstract:

This project explores the basic biology of a newly identified family of molecules that are expressed on antibody-producing B-cells of the immune system. The molecules (FC receptor-like molecules, FCRL 1-5) are expressed on the surface of different types of B-cells and may modulate signaling based on components in their intracellular tails. Importantly, B-cells are responsible for greater than 75% of non-Hodgkin's lymphomas including B-cell chronic lymphocytic leukemia (B-CLL). We have found that four FCRL molecules are expressed by B-CLL cells and at significantly higher levels by indolent CLL cells with mutated antibody genes.

An analysis of 107 samples indicates that the expression pattern of the FCRL2 representative has ~94% concordance with the mutated subtype and can predict time from diagnosis to initial treatment. Because antibody gene sequencing is not routinely performed in hospital laboratories, FCRL2 may serve as a novel prognostic marker for CLL and could help determine which patients have aggressive or indolent disease.

This study will optimize FCRL2 detection on CLL cells and explore the biological basis for its expression in CLL. It is anticipated that this work will contribute to better therapeutic strategies for some of the patients afflicted with B-cell malignancies and other B-cell related disorders, and could help elucidate basic pathogenic defects underlying their disease.