Determining Mutational Status of Immunoglobulin V Genes in Chronic Lymphocytic Leukemia
Determining the clonal origins of malignant B-cells will have an impact on disease understanding and management. In this regard, immunoglobulin variable (V) region gene analysis already is having a significant impact in delineating the tumor cell of origin. It can identify, among other features whether such a cell has undergone somatic mutation, which usually occurs within germinal centres. Remarkably, in chronic lymphocytic leukemia (CLL), the mutational status of V genes has allowed researchers to identify two subsets of disease, one originating from an unmutated B-cell with a markedly poorer disease outcome and the other from a mutated B-cell, which associates with long-term survival. The V gene status in CLL thus provides a robust indicator of disease outcome, which is beginning to shape clinical treatment. This chapter describes in detail the methodology for determining V gene usage in CLL, from acquisition of patient sample to generating the V-gene readout.
Key WordsImmunoglobulin V gene somatic mutation prognosis leukemia
This work was funded by The Leukaemia Research Fund UK, Tenovus UK, Cancer Research UK, and a European Society for Medical Oncology Fellowship (to N.Z.).
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