Abnormal Cells Present in Blood Years before Leukemia Is Diagnosed
The Bottom Line
The Whole Story
Chronic lymphocytic leukemia (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.
Previous research has shown that individuals with an abnormal condition known as monoclonal B-cell lymphocytosis (MBL) have a higher risk of developing CLL than people without this condition. In MBL, small groups of genetically identical B-cells (called clones) develop whose outer-surface proteins are similar to proteins found on CLL cells. MBL is found more often in family members of CLL patients than in the general population, and this condition has been suggested to be a precursor to CLL. However, many questions have remained about the connection between MBL and CLL, such as whether CLL is always preceded by MBL or whether CLL can develop in the absence of MBL.
To investigate these questions, a team that included researchers from the National Cancer Institute, the Food and Drug Administration, and other institutions used data from a group of more than 77,000 people who were participating in a large national study, the nationwide Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. These individuals were all free of cancer when they entered the study, but 129 of them subsequently developed CLL. For 45 of the patients with CLL, the researchers were able to obtain stored cryopreserved blood samples that had been collected up to 6.4 years before the diagnosis of CLL. Using sophisticated laboratory techniques, the researchers detected MBL in the prediagnostic blood samples of 44 of these patients.
"Our findings indicate that MBL is present in virtually all CLL patients prior to full-blown disease," said lead author Ola Landgren, M.D., Ph.D., of NCI's Center for Cancer Research. "This important discovery provides novel insights into the natural history of CLL and will open new fields of investigation for understanding its causes." The risk of developing CLL for individuals with MBL appears to be low--on average, it is estimated that each year, only about one percent of them will develop CLL requiring initiation of therapy, he noted.
The researchers note that their results do not suggest that people should be routinely screened for MBL outside of a clinical trial or a population-based screening study. Nevertheless, according to coauthor Neil Caporaso, M.D., from NCI's Division of Cancer Epidemiology and Genetics, "identifying and studying MBL will provide insight that is not available when studying CLL itself. An important and unanswered question is what causes some individuals with MBL to progress to CLL while others remain disease free. Investigating MBL may help us to determine early risk factors for the disease and allows us to identify the precise molecular changes that occur in these cells that cause them to transform into CLL."
The work underscores the importance of studying family history and progression of disease. Evaluating members of cancer-prone families has been key to identifying and characterizing MBL; current work focuses on trying to identify molecular markers and environmental influences that predict risk and genes that influence CLL development.
The report of this study was published in the New England Journal of Medicine in February 2009.
More summaries of selected scientific advances from NCI-supported research are available at http://www.cancer.gov/aboutnci/servingpeople/advances.