Plasma-based testing as a new paradigm for clinical testing in hematologic diseases

Recent advances in molecular biology have paved the way for the detection of minute quantities of cellular components with robust assays that are amenable for use in clinical laboratories. This review discusses the recently developed series of plasma-based assays that are changing the testing paradigm for hematologic diseases. These tests are based on the concept that a high turnover of neoplastic hematologic cells, relative to normal cells, enriches plasma with tumor-specific DNA, RNA and protein. Plasma-based testing promises to reduce the need for bone marrow biopsy, allow for more frequent and accurate monitoring of changes in bone marrow, allow the detection of more aggressive subclones of the malignant cells and provide a more quantitative means to measure the load of the malignant clone. We present data demonstrating that plasma, in some situations, allows even more sensitive detection than bone marrow cells. Moreover, the lessened impact of dilution by normal cells in plasma permits a distinction between homozygous and hemizygous abnormalities. Unlike solid tumors, currently available data suggest that in hematologic diseases, plasma is superior to cells in detecting molecular abnormalities.