Target of Potent Chronic Leukemia Drug Confirmed in New Study

Like BTK, these molecules are proteins called kinases, and they might be important for CLL-cell survival, the researchers say. "Ibrutinib's lack of selectivity might mean that BTK is not the critical target in CLL, and that future drugs developed for CLL should focus on other molecules," says principal investigator Amy Johnson, PhD, associate professor of medicine in the division of hematology, and an OSUCCC - James researcher. However, the findings, published in the journal Blood, validated BTK inhibition. "This study shows that BTK is an important therapeutic target in CLL," says first author Jennifer Woyach, MD, assistant professor in the division of hematology and an OSUCCC - James researcher. "Inactivating BTK alone delayed CLL development in a mouse model, confirming that BTK is a clinically important target in CLL. This suggests that development of selective BTK inhibitors - in addition to multi-kinase inhibitors like ibrutinib - is reasonable in CLL." To investigate the role of BTK in CLL, Johnson, Woyach and their colleagues used CLL cells from patients and two CLL mouse models, one of which spontaneously develops a malignancy very similar to human CLL. The researchers blocked BTK activity two ways: genetically and pharmacologically, using ibrutinib.