Can LCK Deletion Result in Acceleration of CLL?
Posted: Sunday, November 1, 2020
According to research published in Frontiers in Immunology, the progression of chronic lymphocytic leukemia (CML) may be accelerated in patients who experience an ablation of the tyrosine kinase LCK. Martin R. Müller, MD, PhD, of the University of Tübingen, Germany, and colleagues found that the deletion of LCK resulted in the restoration of B-cell–receptor signaling and the acceleration of disease.
The study used CD5+CD19+ cells from the Eμ-TCL1 mouse model to demonstrate important features of anergic CLL cells, including the impairment of CA2+ mobilization capacity and a reduced presence of serum IgM versus physiologic B cells. The activation of ERK1/2 and NFAT2, a crucial CA2+-dependent transcription factor in lymphocyte development, was also observed. The deletion of NFAT2 can amplify B-cell–receptor signaling and may result in proliferative disease. A high rate of NFAT2 expression was found to be characteristic of indolent CLL cells and to correlate with anergic B-cell receptors. Of note, anergy is a known trait of CLL, the study authors noted.
The LCK knockout model was used to identify the presence of LCK in both physiologic and malignant B cells. A subpopulation of patients with CLL and abnormal B-cell–receptor signaling can be determined from LCK expression. In physiologic B cells, LCK has demonstrated the ability to either augment or suppress B-cell–receptor signaling.
Disclosure: The study authors reported no conflicts of interest.
