Lynne V. Abruzzo, M.D., Ph.D. University of Texas MD Anderson Cancer Center

THERAPY/ PROGNOSTIC

Validation of Prognostic Biomarkers in CLL

Grant awarded in 2004

Abstract:

Although there are promising new treatments for CLL, it is generally incurable. In some patients, the malignant CLL cells accumulate slowly. These patients live for many years and may never require treatment. In other patients, the malignant CLL cells accumulate rapidly. Despite treatment, many of these patients succumb to the disease within a few years. Hematologists have searched for markers that will allow them to predict which patients will have slowly progressing disease and which patients will have aggressive disease that requires treatment in the near future. Traditional markers, such as the number of CLL cells circulating in the blood and how rapidly the CLL cells divide, have been helpful, but are not always accurate.

Recent advances in the field of molecular biology have allowed researchers to identify and measure many genes that distinguish different types of cancer cells (for example, colon cancer and breast cancer) from their normal counterparts. In studies of CLL, researchers have identified hundreds of genes that are expressed at different levels in patients with slowly progressing CLL compared to those with aggressive CLL. We have re-analyzed the data from several studies of CLL using new statistical tests.

Our results suggest that it may be possible to predict whether a patient will have slowly progressing or aggressive CLL by measuring the levels of only a few of these genes. If we are correct, then it would be possible to develop a rapid and reliable blood test to predict whether a patient will have slowly progressing or aggressive CLL. We will use a relatively new laboratory technique, quantitative real-time polymerase chain reaction (QRT-PCR) assay, which measures gene expression levels rapidly and accurately. We will also use new microfluidics technology to perform the QRT-PCR assays. This technology miniaturizes the QRT-PCR assay, so that we can measure many genes simultaneously using only a small amount of blood. Our goal is to develop a rapid and reliable blood test to predict which patients will require treatment soon after they learn that they have CLL, and which patients may never require treatment.