← Back
After treatment and remission

Molecular monitoring

Some leukaemias carry a specific “genetic signature” — such as a fusion gene or a mutation. Measuring that signature regularly during remission is called molecular monitoring. This topic explains in which leukaemias it is used and how.

Last updated: ~3 min read
Two chromosome segments in different colours joined at a glowing point.
Figure 1.A fusion gene works as the leukaemia’s “fingerprint”.

01Short answer

Molecular monitoring means measuring the amount of a leukaemia-specific gene change in blood or bone marrow during remission. The most widely used method is quantitative PCR: it measures the marker (for example BCR::ABL1, PML::RARA, CBFB::MYH11 or an NPM1 mutation) relative to a normal “control” gene. In chronic myeloid leukaemia it is the main test for tracking treatment response. In some acute myeloid leukaemias it is done at set intervals after treatment. A marker that falls gradually and stays low is a good sign, while a repeated rise can signal the doctor to act early. Every result is interpreted with your doctor.

02Simple explanation

Some leukaemias have a genetic signature.

That signature can be measured during remission too.

It is usually measured with quantitative PCR.

The result is often given as a ratio to a control gene.

What matters is change over time.

03Scientific explanation

CML: according to ELN 2020, BCR::ABL1 is measured on the International Scale (IS); ≤0.1% is called a “major molecular response” (MMR), and testing is usually every 3 months.

CBF AML and NPM1: the 2021 ELN MRD consensus recommends molecular monitoring after treatment, for example about every 3 months for 24 months.

APL: according to the NCI, PML::RARA is tracked with a molecular test in acute promyelocytic leukaemia.

Confirmation: the ELN advises confirming a new positive result or a rise with a repeat test.

04What happens in the body?

What is a genetic signature?

In some leukaemia cells two genes are fused (a fusion gene) or one gene carries a mutation. Normal cells do not have this change, so it works as the leukaemia’s “fingerprint”.

How is it measured?

RNA or DNA is taken from blood or marrow. Quantitative PCR counts the copies of the marker and compares them with a control gene present in every cell. This ratio makes it possible to compare results taken at different times.

Quantitative PCR measures the amount of the marker
Figure 2.Quantitative PCR measures the amount of the marker.

In which leukaemias?

Chronic myeloid leukaemia (BCR::ABL1), Ph-positive ALL, acute promyelocytic leukaemia (PML::RARA), AML with inv(16) or t(8;21), and AML with an NPM1 mutation. In other cases MRD may be measured by flow cytometry.

A glass balance with a large glowing sphere on one side and a small one on the other.
Figure 3.The marker is measured as a ratio to a control gene.

How to read the result

The number is judged as a series, not once. A very low or undetectable level is a good sign. Small fluctuations can come from laboratory differences. A repeated rise needs your doctor’s attention.

If there is a rise

A repeat test is usually done. If the rise is confirmed, your doctor discusses further tests and treatment options. Finding it early often means more options.

05From gene marker to result

The steps of molecular monitoring.

Start — A gene change is found at diagnosis.1StartA gene change is found at diagnosis.
Sample — RNA/DNA from blood or marrow.2SampleRNA/DNA from blood or marrow.
Measurement — The marker is quantified.3MeasurementThe marker is quantified.
Series — Results are tracked over time.4SeriesResults are tracked over time.
A precise markerThe leukaemia’s own fingerprint.
A seriesChange is seen in time.
An early decisionMore options.

06Examples of molecular markers (simplified)

MarkerLeukaemiaNote
BCR::ABL1CML, Ph+ ALLMeasured on the International Scale
PML::RARAAcute promyelocytic leukaemiaTracked after treatment
CBFB::MYH11AML, inv(16)Regularly, as planned
RUNX1::RUNX1T1AML, t(8;21)Regularly, as planned
NPM1 mutationAMLRegularly, as planned

* Your doctor sets the schedule and thresholds according to the protocol.

07Key terms

Fusion gene
A new gene formed when two genes join.
Quantitative PCR
A test that measures the amount of a marker.
Control gene
A gene present in every cell, used for comparison.
International Scale (IS)
A common scale for comparing BCR::ABL1 results.
MMR
Major molecular response in CML.
Molecular relapse
A repeated rise in the marker.

08Key points

  • Some leukaemias have a genetic signature.
  • It can be measured in remission.
  • The main method is quantitative PCR.
  • Results are judged as a series.
  • A rise is confirmed with a repeat test.
  • Do not stop medicines yourself.

09Frequently asked questions

Is a molecular test possible in every leukaemia?

No, only when there is a suitable marker.

My result says “not detected” — what does that mean?

The marker was not found within the test’s sensitivity. That is a good sign; follow-up continues.

Why does the number go up and down slightly?

Small fluctuations can be normal. Your doctor looks at the trend.

Can the test be done on blood?

Often yes; in some cases marrow is more sensitive. Your doctor decides.

How long will it be monitored?

It depends on the leukaemia: for years in some, and usually throughout treatment in CML.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Is a molecular test possible in every leukaemia?

  2. My result says “not detected” — what does that mean?

  3. Why does the number go up and down slightly?

  4. Can the test be done on blood?

  5. How long will it be monitored?

My questions

12Sources

  1. Blood, 2021. Heuser M et al. 2021 update on MRD in AML: a consensus document from the ELN MRD Working Party
  2. Blood, 2022. Döhner H et al. Diagnosis and management of AML in adults: 2022 ELN recommendations
  3. National Cancer Institute (NCI). Chronic Myeloid Leukemia Treatment (PDQ®)–Patient Version
  4. National Cancer Institute (NCI). Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version
  5. MedlinePlus (U.S. National Library of Medicine). Genetic Testing
  6. Leukemia & Lymphoma Society (LLS). Minimal/Measurable Residual Disease
  7. Leukemia, 2020. Hochhaus A et al. ELN 2020 recommendations for treating chronic myeloid leukemia
  8. JAMA Oncology, 2017. Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: A Meta-analysis
  9. JAMA Oncology, 2020. Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia: A Systematic Review and Meta-analysis
  10. Lancet Oncology, 2018. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
Last updated: ← Back to the list

Open the interactive site →