Molecular test for the diagnosis and monitoring of leukemia BCR-ABL1 is a molecular test that identifies and, when used quantitatively, measures BCR::ABL1 fusion gene transcripts in blood cells. BCR::ABL1 is a molecular characteristic of most cases of Chronic Myeloid Leukemia (CML), and its identification plays an important role in diagnosis and monitoring the response to treatment.
What is BCR::ABL1? BCR::ABL1 is a fusion gene created as a result of a chromosomal change involving chromosomes 9 and 22. This change leads to the formation of the so-called Philadelphia chromosome (Ph) and creates a protein with continuously active tyrosine kinase activity, which plays an important role in the development of CML. The presence of BCR::ABL1 is one of the main molecular characteristics of CML.
What is the BCR-ABL1 test used for? The test may be used for:
The European LeukemiaNet recommends monitoring BCR::ABL1 mRNA at least every 3 months until a major molecular response is achieved and confirmed; thereafter, intervals may be extended in patients with a stable response.
How is the test performed? The test is usually performed by analyzing BCR::ABL1 RNA from blood cells. The widely used method is:
RT-qPCR Reverse Transcription Quantitative Polymerase Chain Reaction This method:
What type of sample is used? BCR-ABL1 is usually analyzed from peripheral blood. In certain clinical situations, bone marrow material may also be used, depending on the purpose of testing and the physician’s assessment.
What are p210 and p190? There are different forms of the BCR::ABL1 transcript.
BCR::ABL1 p210 The p210 transcript is primarily associated with CML and is the standard form monitored in most patients with CML. The most common variants are:
Approximately 98% of patients with CML express one of these two standard variants.
BCR::ABL1 p190 The p190 transcript is more commonly associated with some cases of acute lymphoblastic leukemia (ALL) and other hematological neoplasms. Therefore, identifying the type of transcript is important for clinical interpretation and subsequent monitoring.
What does a positive result mean? A positive result indicates that the BCR::ABL1 transcript has been identified in the analyzed sample. In the appropriate clinical context, identification of BCR::ABL1 supports the diagnosis of a hematological neoplasm associated with this fusion, particularly CML. The result should be interpreted together with:
What does a negative result mean? A negative result means that the targeted BCR::ABL1 transcript was not detected by the method within its sensitivity limit.
A negative result should not be interpreted separately from the clinical situation. If suspicion of CML remains high, other diagnostic methods or testing for other BCR::ABL1 transcript variants may be required. Guidelines emphasize the importance of using a method capable of detecting relevant transcript variants.
BCR-ABL1 for treatment monitoring One of the most important uses of the test is monitoring patients with CML during treatment. Treatment of CML often includes tyrosine kinase inhibitors (TKIs) that target the activity of the BCR::ABL1 protein. Periodic measurement of BCR::ABL1 levels helps the physician assess the molecular response to treatment.
What is the International Scale (IS)? The International Scale (IS) is a standardized method for reporting BCR::ABL1 levels. Standardization is important because it allows results obtained at different times and in different laboratories to be more comparable. The result is usually reported as: BCR::ABL1 % IS The greater the reduction in BCR::ABL1 levels, the deeper the molecular response.
What is Major Molecular Response – MMR? MMR (Major Molecular Response) is defined as: BCR::ABL1 ≤ 0.1% IS This corresponds approximately to MR3, meaning a 3-log molecular reduction compared with the baseline standard used for the International Scale. Deeper molecular responses may be expressed as:
These categories are used to describe the depth of the molecular response.
Why is monitoring over time important? A single result does not provide all the information. What is particularly important is the trend in BCR::ABL1 over time. The physician may compare results to determine whether the level is: decreasing → response to treatment remaining stable → requires interpretation in the context of therapeutic goals increasing → may require further evaluation Changes should be interpreted by the hematologist, as technical variations in the analysis, timing of testing, and the clinical situation may affect the result.
How often is BCR-ABL1 performed? According to European LeukemiaNet recommendations, molecular monitoring is usually performed at least every 3 months during the initial monitoring phase until a major molecular response is achieved and confirmed. After achieving a stable response, testing may be performed every 4–6 months, depending on the clinical situation. The final testing frequency is determined by the hematologist.
BCR-ABL1 and CML Chronic Myeloid Leukemia (CML) is a hematological disease in which BCR::ABL1 plays a central role in the biology of the disease. For this reason, BCR-ABL1 is one of the most important molecular markers for: Diagnosis → Monitoring → Assessment of treatment response
Is it used only for diagnosis? No. BCR-ABL1 has two main roles:
Diagnosis Identification of BCR::ABL1 may help confirm a neoplasm associated with this fusion.
Monitoring Quantitative measurement of BCR::ABL1 is used to monitor the molecular response during treatment and follow-up.
It is a molecular test that identifies and/or measures BCR::ABL1 fusion gene transcripts, an important marker in CML and certain other hematological neoplasms.
Yes. In most cases, it is performed using peripheral blood.
Yes. Identification of BCR::ABL1 is an important component of the diagnostic evaluation of CML.
Yes. BCR-ABL1 is one of the main tests used for molecular monitoring of patients with CML during treatment.
p210 is the main form of BCR::ABL1 found in most patients with CML.
p190 is another form of BCR::ABL1 that is more commonly associated with some cases of ALL and other hematological neoplasms.
It means that the BCR::ABL1 transcript has been identified. Interpretation depends on the type of transcript and the clinical context.
It means that the targeted transcript was not detected in the analyzed sample within the sensitivity limit of the test.
%IS is the internationally standardized method for reporting BCR::ABL1 levels.
MMR stands for Major Molecular Response and corresponds to BCR::ABL1 ≤ 0.1% IS, or MR3.
No. The result should be interpreted in the context of the molecular response, duration of treatment, and other clinical data.
Usually at least every 3 months during the initial monitoring phase, with longer intervals in patients with a stable response, according to guidelines and the hematologist’s decision.
Yes. Changes in BCR::ABL1 levels over time are a key component of monitoring the molecular response to treatment.
No. The result should be interpreted together with the complete blood count, hematological examinations, cytogenetic testing, and other necessary assessments.
