Digital PCR (dPCR) technology provides support for the road to "cure" of CML
2024-04-28
CML is the abbreviation of chronic myeloid leukemia (CML), also known as chronic myeloid leukemia. It is a malignant tumor of the blood system, accounting for 15% of adult leukemia patients, with an annual global incidence of 1.6 to 2/100,000. Its onset is caused by the BCR-ABL1 fusion gene produced at the ends of chromosomes 9 and 22 in the patient's body, which is why the International CML Day is set on September 22. This year is the 13th International CML Day.

▎CML becomes a curable and controllable "chronic disease"
Although CML is a malignant tumor of the hematopoietic system, its efficacy has undergone a leapfrog change since the advent of tyrosine kinase inhibitors (TKIs), which has significantly changed the prognosis and current status of CML patients. It is regarded as a curable and controllable "chronic disease" like hypertension and diabetes, and can even be stopped through standardized treatment to achieve clinical recovery.
▎CML treatment: Standardized monitoring of efficacy is important
More and more clinical research data show that various TKIs represented by imatinib as first-line treatment drugs have increased the 10-year survival rate of CML patients to 85%~90%. Since TKIs therapy cannot completely eradicate leukemia clones, it was initially believed that treatment needs to continue indefinitely. However, in recent years, CML patients have become more likely to stop treatment. In fact, in clinical trials and real-life populations, approximately 50% of CML patients in stable deep molecular remission (DMR, MR4.0) can safely stop TKI treatment without molecular relapse, thus entering treatment free remission (TFR).
Some patients who achieve sustained deep molecular remission (DMR) for more than 2 years after TKIs treatment can achieve long-term treatment-free remission, i.e. functional cure. Functional cure has become the treatment goal pursued by more and more CML patients. It should be noted that drug discontinuation has strict requirements on DMR levels, post-discontinuation monitoring and follow-up, and it is recommended to be carried out under the guidance of professional physicians.
▎dPCR helps to monitor MRD patients stably and reliably
With the increasing requirements for monitoring BCR-ABL1 transcripts in CML patients, the role of molecular technology in quantifying BCR-ABL1 transcripts has become increasingly important, while the use of cytogenetic analysis methods has gradually decreased due to factors such as low sensitivity and insufficient information provided.
Real-time quantitative PCR (qPCR) is a commonly used method, but it has limitations in quantitative accuracy due to its inherent technical differences. Especially in the monitoring of DMR levels in CML patients, multiple studies have shown that qPCR is not sensitive enough to reliably quantify residual low levels of BCR-ABL1 in patients with deep molecular response (DMR), who may have the opportunity to try to stop tyrosine kinase inhibitor (TKI) treatment. Treatment options rely on the BCR-ABL1 fusion ratio measured at each milestone time point, so BCR-ABL1 levels must be measured.