Unlocking the Secrets of Leukemia

Professor’s Research Supported by $331K NIH Grant

This microscope view shows a proliferation of abnormal white blood cells in a patient with chronic myelogenous leukemia, a form of cancer that affects the bone marrow.

This microscope view shows a proliferation of abnormal white blood cells in a patient with chronic myelogenous leukemia, a form of cancer that affects the bone marrow.

12/23/2011
By Edwin Aguirre

Leukemia is a form of cancer that starts in blood-forming tissues such as the bone marrow and causes abnormally large numbers of white blood cells to be produced and enter the bloodstream.

“Leukemia is a serious disease that causes aberrant proliferation of blood progenitors, ultimately leading to the loss of all blood cell types,” says Asst. Prof. Peter Gaines of the Biological Sciences Department.

The U.S. National Cancer Institute estimates that in 2011 nearly 45,000 Americans will be diagnosed with leukemia; of these, nearly 22,000 will die from it.

Gaines is leading a research effort to identify the molecular mechanisms that cause unique structural features to form in the nuclei of two blood cells that are critical to the body’s immune system — the neutrophils and macrophages. His study also aims to define the roles that proteins enveloping the cells’ nuclei play in orchestrating these structural changes.
 
His work, which is supported by a three-year $331,000 grant from the U.S. National Institutes of Health (NIH), will provide a better understanding of why abnormal structures in the cells’ nuclei and the disrupted expression of nuclear envelope proteins are associated with blood-related cancers, including life-threatening myelodysplasia and myelogenous leukemia. He hopes this research will eventually lead to earlier diagnosis and better detection techniques for these diseases.

“Early diagnosis can be critical to the effectiveness of treatment,” says Gaines.

A Silent Killer

Myelogenous leukemia is one of the most common forms of the disease, says Gaines.

“It is caused by mutant progenitors that normally develop into neutrophils, the primary white blood cell responsible for our ability to fight bacterial and certain fungal infections,” he explains.

The neutrophil is unique compared to all other blood cells in that its nucleus is “lobulated,” a feature thought to facilitate the ability of neutrophils to escape from capillary networks in infected tissues. 

“Interestingly, the emergence of blood neutrophils that lack lobulation of their nuclei is a common trait of myelodysplasia, a disorder that often progresses to myelogenous leukemia,” he says. 

Recent studies by Gaines’s laboratory have demonstrated that a protein, called the “lamin B receptor” (LBR), plays a critical role in causing lobulation in neutrophil nuclei, but the roles for this or any other nuclear envelope protein that might be associated with cancerous or pre-cancerous proliferation of blood cells have not been identified. 

“Our research aims to explore the functions of the LBR and associated nuclear proteins in regulating both the differentiation and function of neutrophils as well as macrophages,” he says. “By understanding how these proteins function during blood cell development, we may increase our understanding of how leukemic mutations affect not only blood cell proliferation but also structural maturation. These studies are unique because most studies of leukemia focus on the gene expression profile of cells, while the function of nuclear structural proteins has been largely ignored.”