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Testing of blood specimens may detect abnormal white blood cells in patients years before the chronic form of lymphocytic leukemia (CLL) develops, according to research recently published in the New England Journal of Medicine. The finding may lead to a better understanding of cellular changes that characterize the earliest stages of the disease and how it progresses.

Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and the FDA, led the study, which was co-authored by two researchers with Quest Diagnostics (Madison, New Jersey), Maher Albitar, MD, medical director and chief of research and development, hematology and oncology, and Wanlong Ma, research and development manager, hematology and oncology.

The study, titled "B-Cell Clones as Early Markers for Chronic Lymphocytic Leukemia," was accompanied by the editorial "The Secret Lives of Monoclonal B Cells," written by Robert Vogt Jr., PhD, and Robert Kyle, MD.

For the study, Albitar and Ma developed a method to identify abnormal B-cell clones in blood specimens. Quest said it plans to use a similar approach to develop tests that may one day be used by physicians as an aid in identifying patients who will develop CLL.

"We searched for tumor cells by performing a sophisticated form of flow cytometry as well as molecular testing on frozen samples of whole blood and blood plasma," Albitar said. "The findings of this study lead to better understanding of biological processes underlying the development of CLL, and give us hope that in the future we will be able to develop new testing techniques to look at blood from patients with abnormal cells and distinguish those who will develop overt cancer from those who will not."

CLL is a blood cancer that usually progresses slowly over many years. In this disease, abnormal white blood cells called B-cells accumulate in the blood and the bone marrow. The lymph nodes, spleen, and other organs may also be affected. Although CLL is the most common form of leukemia in adults in Western countries, little is known about what causes the disease or how it develops, Quest noted.

Previous research by the NCI/FDA team and others showed that some family members of CLL patients can have B-cells in their blood that have outer-surface proteins that are similar to proteins found on CLL cells. This abnormal condition, known as monoclonal B-cell lymphocytosis (MBL), occurs in over 10% of CLL family members and in about 3% to 5% of healthy adults over the age of 50, suggesting it might be a precursor of CLL.

In the current study, the research team identified 45 individuals among the more than 77,000 participants in the nationwide Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial who were cancer-free upon entering the trial, were later diagnosed with CLL, and had frozen blood samples available for analysis that had been collected upon their enrollment in PLCO. Using sophisticated laboratory techniques developed by Quest to analyze the blood samples, the researchers found that 44 of the 45 CLL patients had MBL between six months to more than six years prior to their CLL diagnosis. Prior research shows that the MBL cells were identified by examining cell-surface proteins, or CLL markers, using a method called flow cytometry, and by using molecular techniques to confirm the presence of certain rearranged genes, known as immunoglobulin heavy variable (IGHV) group genes, found in CLL. In 41 patients, MBL was confirmed by both methods, Quest said.

"Quest Diagnostics is the leader in cancer testing, and this study demonstrates the commitment of our science and innovation team to advancing cancer research," said Surya Mohapatra, PhD, CEO and chairman of Quest Diagnostics.

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