Introduction
Dr. Terence J. Hamblin’s co-discovery with Dr. Nicholas Chiorazzi of the clinical significance of unmutated and mutated Ig genes in CLL allowed for the separation of patients into two major clinical groups: indolent clinical course and aggressive clinical course. Dr. Hamblin’s research interests developed out of an early 1972 paper on mononucleosis, which led to a lifelong interest in cold agglutinin disease. This led him to VH Ig genes and the discovery of shared idiotypes in cold agglutinin disease. Subsequently, he observed the relationship of unmutated Ig genes to patients with trisomy 12 and the relationship of mutated Ig genes to patients with 13q14 deletion. This observation led to the conclusion that unmutated Ig genes in CLL are associated with a more aggressive clinical behavior in terms of time to treatment and overall survival. The role of CD38 expression led to the further observation of occasional discordance between these biomarkers.