BCR::ABL1 (Philadelphia Chromosome) in Chronic Myeloid Leukemia

by Kamran Mirza MBBS PhD FCAP
April 3, 2026

If your blood test or bone marrow report mentions BCR::ABL1 or the Philadelphia chromosome, these refer to the same genetic change — a mistake in the DNA of a blood-forming cell that causes it to produce a new, abnormal protein. That protein drives the uncontrolled growth of white blood cells seen in chronic myeloid leukemia (CML). BCR::ABL1 is not just a marker for the disease — it is the cause of it, the target of treatment, and the thing your medical team measures at every follow-up visit to check how well treatment is working. Understanding what this test looks for and how to read the numbers that come back over time makes a real difference in living with CML.

What the test looks for

Every cell in your body contains 23 pairs of chromosomes. Chromosomes are long, tightly coiled strands of DNA — the instructions your cells use to grow, divide, and do their jobs. In CML, a mistake happens in a single blood-forming cell in the bone marrow. A piece of chromosome 9 and a piece of chromosome 22 break off and switch places. This type of swap is called a translocation.

When the piece of chromosome 9 lands on chromosome 22, it brings a gene called ABL1 with it. That gene lands right next to a gene called BCR, which was already sitting on chromosome 22. The two genes become joined end-to-end, like two separate sentences accidentally merged into one. The result is a brand new, abnormal gene called BCR::ABL1 — a fusion gene, meaning a gene made by fusing two genes that do not normally belong together.

Chromosome 22, which carries this fusion gene, is shorter than normal because it has given away some of its material. This shortened chromosome is called the Philadelphia chromosome — named after the city where scientists first spotted it in 1960.

The BCR::ABL1 fusion gene produces an abnormal protein. In a healthy cell, the normal ABL1 protein acts like a switch — it briefly turns on to signal the cell to grow and divide, then turns off again. The abnormal BCR::ABL1 protein is permanently stuck in the on position. It never stops telling blood-forming cells to grow. This is what causes the bone marrow to overproduce white blood cells in CML.

BCR::ABL1 testing looks for this fusion gene and measures how much of it is still active. Depending on the type of test, it can confirm whether the fusion is present, identify which version of it you have, and track how much remains as treatment takes effect.

Why is the test done

BCR::ABL1 testing in CML has two equally important roles: making the diagnosis and tracking treatment response over time.

At diagnosis, finding the Philadelphia chromosome or BCR::ABL1 fusion gene is essential — this finding defines CML. This specific genetic change causes no other common blood cancer, so confirming it is the first step toward choosing the right treatment.

During treatment, BCR::ABL1 testing becomes the main way to measure how well the therapy is working. The drugs used to treat CML work by blocking the abnormal BCR::ABL1 protein. As they do their job, the amount of BCR::ABL1 detectable in the blood falls. Checking this level regularly tells the medical team whether the treatment is having the expected effect, whether any early signs of resistance are appearing, and, in patients who do very well, whether it might be safe to try stopping treatment altogether.

How the test is performed

Three different types of tests are used to detect and monitor BCR::ABL1. Each one is suited to a different stage of care.

Chromosome testing (karyotype)

A karyotype is a test that examines the complete set of chromosomes in cells taken from a bone marrow sample. The laboratory allows the cells to grow briefly, then stops them at the moment when chromosomes are most visible under the microscope. A technician photographs the chromosomes and looks for the shortened chromosome 22 — the Philadelphia chromosome.

This test can detect the Philadelphia chromosome in about 95% of CML cases. It can also spot other chromosome changes that may affect how the disease behaves. The limitation is that it is not very sensitive — it cannot detect very small amounts of residual disease once treatment has reduced the leukemia to low levels.

FISH testing

Fluorescence in situ hybridization — usually called FISH — uses tiny pieces of DNA tagged with coloured dyes. These tagged pieces are designed to stick only to the BCR and ABL1 gene regions. In a normal cell, the two colors appear as separate dots. In a CML cell, where the two genes have been joined, the two colored dots appear merged — confirming the fusion.

FISH is more sensitive than chromosome testing and can be done on blood or bone marrow. It is most useful for diagnosis or when chromosome testing gives an unclear result. Like chromosome testing, it cannot pick up very small traces of disease during treatment monitoring — for that, a different test is needed.

PCR blood test

PCR — polymerase chain reaction — is by far the most sensitive test for BCR::ABL1 and is the main tool used to monitor treatment. It works by detecting the activity of the BCR::ABL1 fusion gene in a blood sample. When the fusion gene is active inside a cell, it produces a messenger molecule called RNA. PCR measures the amount of this messenger RNA in the blood, which reflects the number of CML cells that are still present and active.

PCR can detect BCR::ABL1 at levels thousands of times lower than those that chromosome testing or FISH can detect. This is why it is used for ongoing monitoring — it can track the slow, steady fall in leukemia activity as treatment works, and catch very early signs of relapse. It requires only a routine blood draw, with no bone marrow sample needed for regular follow-up.

Resistance mutation testing

If the BCR::ABL1 level stops falling or starts to rise during treatment, an additional test is performed. This test reads the genetic code of the BCR::ABL1 protein to look for small changes — called resistance mutations — that are making the protein harder for the treatment drug to block. Different resistance mutations respond to different drugs. Knowing which mutation is present tells the medical team which drug to switch to. For example, a mutation called T315I blocks most standard CML drugs but responds to specific third-generation options.

How results are reported

At diagnosis

At the time of diagnosis, test results are reported as positive or negative. A positive result confirms the BCR::ABL1 fusion gene is present. The chromosome testing report may use a notation like t(9;22)(q34;q11.2) — this is simply the technical shorthand for the translocation between chromosomes 9 and 22. FISH and PCR reports will each describe the fusion in their own format.

The initial PCR test also identifies your transcript type — the specific version of the BCR::ABL1 fusion gene you have. The most common types are called e13a2 and e14a2. This matters because all future PCR monitoring must measure the same version to give reliable, comparable results over time.

During treatment: the BCR::ABL1 percentage

Once treatment begins, your BCR::ABL1 level is reported as a percentage. This is written as BCR::ABL1^IS — the IS stands for International Scale, a shared system that allows laboratories worldwide to report results in the same way, enabling comparison.

The percentage represents the level of activity of the BCR::ABL1 gene relative to the average level observed in untreated patients at diagnosis, which is set at 100%. As treatment works, the percentage falls. A 10% result means the leukemia activity is one-tenth of its initial level. A result of 0.01% means it is ten thousand times lower than the starting level.

It is important to understand what this percentage does not mean. It is not the percentage of your blood cells that are cancerous. It is a measure of gene activity, and a very small number is a very good sign.

Doctors use specific targets — called milestones — to check whether treatment is working on schedule:

BCR::ABL1^IS ≤10% by 3 months. The first milestone. Reaching this level within three months of starting treatment is a good early sign. Patients who reach it tend to do better in the long run.
BCR::ABL1^IS ≤1% — Major Molecular Response (MMR). This means at least 99% of the original leukemia activity has been eliminated. It is the main ongoing treatment goal for most patients. Most people reach MMR within 12 to 18 months on effective therapy.
BCR::ABL1^IS ≤0.01% — Deep Molecular Response (MR4). A much deeper reduction — leukemia activity is now 10,000 times lower than the starting level. Reaching this level opens the door to eventually trying to stop treatment safely.
BCR::ABL1^IS ≤0.0032% — MR4.5. An even deeper response. Sustaining this level for at least two years is typically required before treatment discontinuation is considered.
Undetectable — Complete Molecular Response (CMR). No BCR::ABL1 is found in the blood sample at all. This is the deepest measurable response. It does not necessarily mean every CML cell is gone — but it means the test cannot find any remaining activity.

What the result means

BCR::ABL1 positive at diagnosis

A positive result at diagnosis confirms CML. For most patients diagnosed in the chronic phase — the earliest and most common stage — this leads directly to highly effective treatment. The outlook for people with CML treated in the modern era is very good. Most people treated in the chronic phase can expect a normal or near-normal life expectancy if they respond well to treatment and continue it as prescribed.

The transcript type identified at diagnosis (e13a2 or e14a2) is recorded so that all future PCR tests use the same measurement target. This is a technical step, but an important one — it means each follow-up result can be accurately compared to the last.

Meeting the treatment milestones

Reaching each milestone on schedule is a sign that treatment is working well. The three-month milestone — BCR::ABL1^IS ≤10% — is the most important early check. Patients who reach it are more likely to maintain a good long-term response.

Reaching major molecular response (≤1%) is the standard long-term goal. Patients who sustain this level have very low rates of disease getting worse and can generally continue their treatment indefinitely with excellent outcomes.

Reaching and sustaining a deep molecular response — MR4 or MR4.5 — makes it possible to discuss stopping treatment. This is called treatment-free remission. It matters because these drugs are taken every day, can cause side effects, and are a significant long-term commitment. About 40 to 60% of patients who stop treatment after a sustained deep response stay in remission without any medication. Those whose leukemia returns almost always respond quickly when treatment is restarted. Attempting discontinuation does not harm long-term outcomes.

If the level does not fall as expected, or starts to rise

If BCR::ABL1^IS does not meet the expected milestones or increases after a period of good control, the medical team will investigate why. The two most common reasons are not taking the medication consistently as prescribed, and the development of resistance — meaning the CML cells have acquired a change that makes the drug less effective at blocking the BCR::ABL1 protein.

Resistance mutation testing is used to identify whether a specific change in the BCR::ABL1 protein is responsible. If a resistance mutation is identified, the treatment can be switched to a drug that is more effective at blocking that specific version of the protein. A rising level confirmed on two consecutive tests, or a level above an agreed threshold, should prompt a conversation with your hematologist about next steps.

BCR::ABL1 undetectable

An undetectable result is the deepest response the test can measure. It does not mean the leukemia is permanently gone — in most patients, a very small number of CML cells remain even when PCR finds nothing. But sustaining this level of response over time is associated with excellent long-term outcomes and is the foundation for treatment-free remission.

The drugs that target BCR::ABL1

The drugs used to treat CML are called tyrosine kinase inhibitors, or TKIs. A tyrosine kinase is a type of protein that sends signals inside cells, telling them to grow. The BCR::ABL1 protein is one of these, and it is permanently stuck in the on position. TKIs work by binding to the BCR::ABL1 protein like a key in a lock, blocking it from sending its signal. Taken as daily tablets or capsules, TKIs do not cure CML in most patients — but they control it so effectively that most people can live normal lives while taking them.

Three generations of TKIs are available:

First generation: imatinib (Gleevec / Glivec). The first TKI was developed for CML and introduced in the early 2000s. It transformed CML from a life-threatening condition into a manageable one. Imatinib remains highly effective for many patients and is now available as a lower-cost generic in many countries.
Second generation: dasatinib (Sprycel), nilotinib (Tasigna), and bosutinib (Bosulif). More powerful than imatinib and effective against many — though not all — resistance mutations. They may be preferred for patients at higher risk or for those who want to achieve a deep molecular response more quickly to pursue treatment-free remission.
Third generation: ponatinib (Iclusig) and asciminib (Scemblix). Developed for patients whose CML has stopped responding to earlier drugs, including those with the T315I resistance mutation. Asciminib works by blocking a different part of the BCR::ABL1 protein than all previous TKIs, making it effective even when other drugs have failed. Ponatinib is also active against T315I but carries a higher risk of cardiovascular side effects that require careful monitoring.

The choice of TKI depends on your overall health, any other medical conditions you have, the specific resistance mutation present (if any), and your treatment goals. Your hematologist will explain which option is most suitable for your situation.

BCR::ABL1 in other blood cancers

BCR::ABL1 is occasionally found in blood cancers other than CML. It is present in about 25% of adult cases of B-cell acute lymphoblastic leukemia (B-ALL) — a different and more aggressive disease than CML. In B-ALL, TKIs are used alongside intensive chemotherapy rather than on their own, and stem cell transplantation is considered more often. If your report identifies BCR::ABL1 in the context of B-ALL rather than CML, your treatment team will explain what this means for your specific situation.

What happens next

For patients newly diagnosed with CML in the chronic phase, treatment with a TKI usually begins within days to weeks of diagnosis. Your hematologist will discuss which TKI is right for you based on your health, your risk level, and your goals — including whether treatment-free remission is something you want to work toward.

Once treatment starts, BCR::ABL1 PCR testing is done regularly — typically every three months in the first year, and every three to six months once a stable response has been achieved. Each result is compared to the milestones and to previous results. Your hematologist will tell you what each result means and whether you are on track.

If your level is not falling as expected, or if it rises after a period of good control, resistance mutation testing will be arranged and a change of medication discussed.

If you reach and sustain a deep molecular response — typically MR4.5 for at least two years — your hematologist will discuss whether it is appropriate to try stopping treatment under close supervision. Monitoring becomes more frequent during and after any discontinuation attempt to catch early signs of return.

If you have been diagnosed in the blast phase, or if your disease has progressed from the chronic phase, your hematologist will explain the more intensive treatment approach needed and discuss all available options.

Questions to ask your doctor

Which transcript type do I have — e13a2 or e14a2 — and does it affect my treatment or monitoring?
What is my current BCR::ABL1^IS result, and am I meeting the expected milestones?
Which TKI are you recommending, and why is it the best choice for me?
How often will my BCR::ABL1 level be tested, and what result would lead to a change in treatment?
If my level rises, will resistance mutation testing be performed to determine why?
Am I on track toward a deep molecular response, and could treatment-free remission be a goal for me?
Are there any clinical trials I should know about?