Discover all of the different techniques and tools that might be used to assess response to treatment in blood cancers.
Cancers that come from B or T cells (lymphomas, myeloma, ALL and CLL) can be tracked using the gene sequences of their immune receptors. These sequences, sometimes described as “barcodes” are unique to each patient and each cancer, but the test used to identify and track them is universal – no customization is needed as in ASO-PCR (see below).
Next-generation sequencing of immune receptor genes (NGS) allows increased sensitivity
too – this method can detect MRD at levels as low as 1 cancer cell per 1 million total white blood cells.
Some blood cancers (e.g., CML) are caused by the rearrangement of chromosome segments and the formation of a cancer-causing fusion protein. In these diseases, MRD can be detected by counting how many copies of the instructions for the fusion protein (called “transcripts”) are present in the body. Real-time quantitative polymerase chain reaction (RQ-PCR) accomplishes this using short pieces of DNA called “primers” and a machine that can copy and count transcripts. RQ-PCR can detect cancer cells at a level as low as about 1 in 100,000 white blood cells.
Allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) is a variation of RQ-PCR. For cancers that do not have a stereotypical chromosome fusion, patient-specific primers are required to carry out the RQ-PCR reaction. Figuring out how to make these primers takes a lot of time and can be expensive. ASO-PCR can detect cancer cells at a level as low as about 1 in 100,000 white blood cells.
Multicolor flow cytometry (MFC) identifies and counts cancer cells based on the presence of certain combinations of protein markers on the cells’ surfaces. Antibodies tagged with fluorescent dyes of different colors are mixed with a blood or bone marrow sample and then a laser is used to measure how many cells display the combination of colors characteristic of a certain type of cancer. The more colors that are used, the more sensitive flow cytometry is. Generally, at least four colors are used for MRD testing, which allows for detection of cancer cells at a level as low as 1 in 10,000 white blood cells. Fewer colors may be used for less sensitive testing.