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Levels of Molecular Response

Until recently the ultimate goal for CML patients treated with TKI therapy was to achieve a ‘PCR negative’ result, also known as a Complete Molecular Response (CMR). However, the use of the word ‘complete’ is now considered to be misleading because it is often interpreted to mean that there has been a total eradication of disease. Recently, international CML experts and clinical groups have agreed to stop using the term CMR replacing it with MR followed by a log reduction number, as in the definition on the next page.

% of BCR-ABL1 detected byqRT-PCR testing Equivalent Log reduction from 100% IS
0.1% MR3
0.01% MR4
0.0032%  MR4.5
0.001%  MR5




Why results may differ between testing laboratories

In its present form, q-PCR testing is technically challenging to perform requiring a high level of skill, a consistent method of sample collection and timely delivery to the laboratory. Several factors can adversely influence a result, which often makes it difficult to be confident that

it is an accurate reflection of the actual level of residual disease.
Factors include:

  • The quality of the sample, also related to time taken for the sample to reach the lab
  • Adequate amounts of a control gene – there should be at least 10,000 transcripts in a sample
  • The control gene used—ABL1, GUSB, BCR or other
  • The method a lab uses to extract mRNA, related to the chemicals and type of equipment used

Even if the method used is consistent, the quality of a sample and the efficient extraction of mRNA are variable. Results, even from the same laboratory, may fluctuate up as well as down. Doctors are only likely to recommend a change of treatment if there is a rise in the % of BCR-ABL1 transcripts from 2 or 3 consecutive q-PCR results generated from samples containing adequate numbers of control gene transcripts such as ABL1 or BCR.