Albert Einstein Cancer Center

Dr. Chiorazzi and his team study human B lymphocytes in health and disease. Current research focuses on defining and characterizing signals from the microenvironment that permit survival and expansion of chronic lymphocytic leukemia B cells, in particular those signals emanating from the leukemic B cell's receptor for antigen (BCR).

The team has determined that the BCRs of CLL patients are restricted in gene segment use and amino acid structure, leading to the hypothesis that antigens promote CLL and may alter clinical course. The data suggest that these antigens are similar between patients and are both foreign (e.g., microbial) and autologous molecules.

In addition the team has divided patients with CLL into subgroups based on features of the BCR: the presence or absence of somatic mutations in IgV genes delineates two broad subgroups that can be further stratified into smaller sets of cases based on striking amino acid structural similarity in the BCR. These distinctions are of major clinical relevance since patients in such subgroups experience dramatically different clinical courses, with median survival times of more than 25 years, often without therapy, versus 6-7 years, despite therapy. The manner by which IgV gene mutations lead to these differences in clinical course remains unclear, although (auto)antigen-binding is a possibility. Therefore, precisely defining the antigens recognized by CLL cells will help understand the cause of and develop novel treatments for this currently incurable disease.