B-cell chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western societies.1 CLL cases can be subgrouped into two types, aggressive or indolent, defined as cases that express high levels of Zeta-chain-associated protein kinase 70 (ZAP70) and unmutated immunoglobulin heavy-chain variable-region genes (IGHV), or low to negligible ZAP70 and mutated IGHV. Chromosomal aberrations can be identified in more than 80% of patients.1 The most frequent genetic alterations include deletion/inactivation of 13q14 (>50%), deletion of 11q22–23 (18%), trisomy of 12 (12–16%) and deletion 17p (7–10%).1
Trisomy 12 identified using Fluorescent In Situ Hybridization (FISH)
From the UC San Diego Moores Cancer Center, La Jolla, CA.
ABSTRACT: The B-cell receptor (BCR) complex and its associated protein tyrosine kinases play a critical role in the development, proliferation, and survival of normal or malignant B cells. Regulated activity of the BCR complex promotes the expansion of selected B cells and the deletion of unwanted or self-reactive ones. Compounds that inhibit various components of this pathway, including spleen tyrosine kinase, Bruton’s tyrosine kinase, and phosphoinositol-3 kinase, have been developed. We summarize the rationale for use of agents that can inhibit BCR signaling to treat patients with either indolent or aggressive B-cell lymphomas, highlight early clinical results, and speculate on the future application of such agents in the treatment of patients with various B-cell lymphomas.
NCI funding continues work focused on chronic lymphocytic leukemia
An international consortium of scientists studying chronic lymphocytic leukemia (CLL), based at the University of California, San Diego School of Medicine, has been awarded a 5-year, $20 million grant by the National Cancer Institute, part of the National Institutes of Health. The grant is the second renewal of funding for a broad-based effort designed to better understand the pathology of CLL – the most common form of leukemia in the Western world – and develop new drugs and treatments.
Magnified blood smear showing darker CLL cells.
“This funding allows us to continue critical research that has already produced substantial, new insights into how and why CLL develops and progresses differently in patients,” said Thomas J. Kipps, MD, PhD, professor of medicine in the UCSD School of Medicine, deputy director of research at UC San Diego Moores Cancer Center and director of the Chronic Lymphocytic Leukemia Research Consortium (CRC). “Our work has revealed new targets and approaches for both mitigating the disease and perhaps eventually preventing it.”