Abnormal cells in the blood exist years before leukemia is diagnosed

Maryland, February 14: Researchers have found that abnormal white blood cells can be present in patients’ blood more than six years prior to the diagnosis of a chronic form of lymphocytic leukemia.

The study was conducted by researchers at the National Cancerdefine Institute (NCI), part of the National Institutes of Health, and the U.S. Food and Drug Administration.

"This finding emphasizes the need to better define predictors of cancer development," said NCI Director John E. Niederhuber, M.D. "Identifying the earliest indicators of cancer gives researchers an opportunity to study the window from the prediagnostic state to the transformation to disease. This may help define risk factors and may allow for the discovery of novel molecular targets for treatment of the disease."

Chronic lymphocytic leukemia (CLL) is a blood cancer that usually progresses slowly over many years. 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 percent of CLL family members and in about 3 percent to 5 percent 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 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. 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 genesdefine, known as immunoglobulin heavy variable (IGHV) group genes, found in CLL. In 41 patients, MBL was confirmed by both methods.

"Our findings indicate that MBL is present in virtually all of CLL patients prior to full-blown disease," said lead author Ola Landgren, M.D., Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics.

Ola Landgren said, "This important discovery provides novel insights into the natural history of CLL and will open new fields of investigation for understanding its causes."

"Next, it will be important to isolate MBL cells and to conduct additional molecular analyses," says Gerald Marti, M.D., Ph.D., of the FDA’s Center for Biologics Evaluation and Research, another study author. "This will provide insight into the differences in these cells that may influence why some transform into CLL whereas other do not."

The study was published in the Feb. 12, 2009, issue of the New England Journal of Medicine.