Molecular Testing, MMR, and CMR
Molecular testing (also called quantitative polymerase chain reaction or QPCR) is the most sensitive test given to people with chronic myeloid leukemia (CML). It can be used both to determine how well you are responding to treatment as well as to help diagnose CML in the first place.
QPCR is used to identify a major molecular response (MMR) or a complete molecular response (CMR). QPCR tests measure amounts of leukemia cells too small to be detected by cytogenetic tests. While cytogenetic testing can detect 1 CML cell from a sample of 20 to 500 cells, molecular testing can detect 1 CML cell among 1 million cells.
For molecular testing, a blood or bone marrow sample is used to count the molecular signals (called
BCR-ABL transcripts) that lead to the growth of leukemia cells.
The first objective of molecular testing is what's called a major molecular response, or MMR—signaling a dramatically reduced number of leukemic cells. The goal is to get to the point where even this most sensitive of tests can detect no leukemic cells. That's called a complete molecular response or CMR.
Molecular Testing: A Closer Look
When your treatment is working, the percentage of Ph+ cells may become undetectable by other tests. Molecular testing, which can be used to help diagnose CML, can also determine how well you are responding to treatment. This type of test is the most sensitive available to people with CML.
||Quantitative polymerase chain reaction
||A sensitive blood or bone marrow test that can detect as few as 1 leukemic cell among 1 million normal cells
If your molecular test shows you are responding to treatment, it's very encouraging. But it doesn't mean you are cured. CML is a chronic disease that does not go away. That is why it is so important to stay on treatment and keep getting tested to make sure your treatment continues to work.
How often will you have a molecular test?
- At diagnosis: Treatment guidelines recommend that molecular testing begin when you are diagnosed with CML.
- Every 3 to 6 months: Molecular tests should be done every few months to evaluate the effectiveness of your treatment.
What do QPCRs tell you and your doctor?
If you've already achieved a complete cytogenetic response (CCyR), molecular tests will continue to tell you and your doctor how your treatment is working. Your doctor will compare your first test result to your follow-up
The results can also help your doctor evaluate how you may respond to treatment over time. Good results mean you are responding to therapy.
Poor results mean you may be losing response, which may be an early warning sign of resistance to your current treatment. In a case of resistance, your doctor will likely perform additional tests to confirm the loss of response, and together you can discuss alternative CML treatment options.
How molecular tests are measured: the language of log reductions
Molecular test results are some of the most complicated of all CML test numbers, so ask your doctor to
Results are often reported as "log reductions." Each "log" means that you have 10 times fewer molecular signals than you had at your first molecular test (the molecular signals, called BCR-ABL transcripts, tell your cells to produce BCR-ABL proteins).
The greater the log reduction, the greater the reduction of BCR-ABL transcripts in your body (see table).
||How much are my BCR-ABL transcripts reduced?
||What percentage of my BCR-ABL transcripts remain?
A major molecular response is a reduction of 3 logs or more.
A complete molecular response means that no BCR-ABL transcripts were detected. It doesn't mean that you are cured because even molecular tests are not sensitive enough to detect very low levels of these signals.