Professor, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, USA
CLECL1-expressing, recently born chronic lymphocytic leukemia cells: A small but dangerous fraction of the leukemic clone
Host: D. Efremov
Like other cancers, chronic lymphocytic leukemia (CLL) develops by the acquisition of genomic
abnormalities in an individual or small numbers of normal cells. Likewise, disease progression
occurs by the expansion of neoplastic subclones that have acquired additional, deleterious
mutations. Since permanent genetic changes occur during DNA replication, the newly-born/
divided (pre)cancerous fraction can be considered a dangerous subset.
In CLL, we have shown that the most recently-born fraction contains the only cells that express
activation induced deaminase (AID) and that have the highest levels of reactive oxygen
species (ROS), two documented DNA mutators, making these cells more likely to develop new
genomic mutations upon DNA replication. Moreover, we have found that the most recently-
born cells are able to create/expand Th2 cells from naïve and committed T cells. Remarkably,
IL-4 made by these Th2 cells is more effective at preventing apoptosis in the most recently
born CLL cells. Based on these findings, we have sought a membrane molecule that would
identify those cells in the recently born fraction that have the above features, finding that
CLECL1-expressing, recently born CLL cells do so. We will present these findings and discuss
the possibility of targeting these cells as a new therapeutic possibility in CLL.
International Seminar Programme
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