Chronic Myeloid Leukemia

What is leukemia?

From: MedlinePlus, National Library of Medicine

Leukemia is a term for cancers of the blood cells. Leukemia starts in blood-forming tissues such as the bone marrow. Your bone marrow makes the cells which will develop into white blood cells, red blood cells, and platelets. Each type of cell has a different job:

• White blood cells help your body fight infection
• Red blood cells deliver oxygen from your lungs to your tissues and organs
• Platelets help form clots to stop bleeding

When you have leukemia, your bone marrow makes large numbers of abnormal cells. This problem most often happens with white blood cells. These abnormal cells build up in your bone marrow and blood. They crowd out the healthy blood cells and make it hard for your cells and blood to do their work.

What is chronic myeloid leukemia (CML)?

From: MedlinePlus, National Library of Medicine

Chronic myeloid leukemia (CML) is a type of chronic leukemia. "Chronic" means that the leukemia usually gets worse slowly. In CML, the bone marrow makes abnormal granulocytes (a type of white blood cell). These abnormal cells are also called blasts. When the abnormal cells crowd out the healthy cells, it can lead to infection, anemia, and easy bleeding. The abnormal cells can also spread outside the blood to other parts of the body.

CML usually occurs in adults during or after middle age. It is rare in children.

What causes chronic myeloid leukemia (CML)?

From: MedlinePlus, National Library of Medicine

Most people with CML have a genetic change called the Philadelphia chromosome. It's called that because researchers in Philadelphia discovered it. People normally have 23 pairs of chromosomes in each cell. These chromosomes contain your DNA (genetic material). In CML, part of the DNA from one chromosome moves to another chromosome. It combines with some DNA there, which creates a new gene called BCR-ABL. This gene causes your bone marrow to make an abnormal protein. This protein allows the leukemia cells to grow out of control.

The Philadelphia chromosome isn't passed from parent to child. It happens during your lifetime. The cause is unknown.

Who is at risk for chronic myeloid leukemia (CML)?

From: MedlinePlus, National Library of Medicine

It is hard to predict who will get CML. There are a few factors that could raise your risk:

• Age - your risk goes up as you get older
• CML is slightly more common in men
• Exposure to high-dose radiation

What are the symptoms of chronic myeloid leukemia (CML)?

From: MedlinePlus, National Library of Medicine

Sometimes CML does not cause symptoms. If you do have symptoms, they can include:

• Feeling very tired
• Weight loss for no known reason
• Drenching night sweats
• Fever
• Pain or a feeling of fullness below the ribs on the left side

How is chronic myeloid leukemia (CML) diagnosed?

From: MedlinePlus, National Library of Medicine

Your health care provider may use many tools to diagnose CML:

• A physical exam
• A medical history
• Blood tests, such as a complete blood count (CBC) with differential and blood chemistry tests. Blood chemistry tests measure different substances in the blood, including electrolytes, fats, proteins, glucose (sugar), and enzymes. Specific blood chemistry tests include a basic metabolic panel (BMP), a comprehensive metabolic panel (CMP), kidney function tests, liver function tests, and an electrolyte panel.
• Bone marrow tests. There are two main types - bone marrow aspiration and bone marrow biopsy. Both tests involve removing a sample of bone marrow and bone. The samples are sent to a lab for testing.
• Genetic tests to look for gene and chromosome changes, including tests to look for the Philadelphia chromosome

If you are diagnosed with CML, you may have additional tests such as imaging tests to see whether the cancer has spread.

What are the phases of chronic myeloid leukemia (CML)?

From: MedlinePlus, National Library of Medicine

CML has three phases. The phases are based on how much the CML has grown or spread:

• Chronic phase, where less than 10% of cells in the blood and bone marrow are blast cells (leukemia cells). Most people are diagnosed in this phase, and many do not have symptoms. Standard treatment usually helps in this phase.
• Accelerated phase, 10% to 19% of the cells in the blood and bone marrow are blast cells. In this phase, people often have symptoms and standard treatment may not be as effective as in the chronic phase.
• Blastic phase, where 20% or more of the cells in the blood or bone marrow are blast cells. The blast cells have spread to other tissues and organs. If you have tiredness, fever, and an enlarged spleen during the blastic phase, it is called a blast crisis. This phase is harder to treat.

What are the treatments for chronic myeloid leukemia (CML)?

From: MedlinePlus, National Library of Medicine

There are several different treatments for CML:

• Targeted therapy, which uses drugs or other substances that attack specific cancer cells with less harm to normal cells. For CML, the drugs are tyrosine kinase inhibitors (TKIs). They block tyrosine kinase, which is an enzyme that causes your bone marrow to make too many blasts.
• Chemotherapy
• Immunotherapy
• High-dose chemotherapy with stem cell transplant
• Donor lymphocyte infusion (DLI). DLI is a treatment that may be used after a stem cell transplant. It involves giving you an infusion (into your bloodstream) of healthy lymphocytes from the stem cell transplant donor. Lymphocytes are a type of white blood cell. These donor lymphocytes may kill the remaining cancer cells.
• Surgery to remove the spleen (splenectomy)

Which treatments you get will depend on which phase you are in, your age, your overall health, and other factors. When the signs and symptoms of CML are reduced or have disappeared, it is called remission. The CML may come back after remission, and you may need more treatment.

Genetic causes described in the linked summary

From: MedlinePlus Genetics

Chronic myeloid leukemia is caused by a rearrangement (translocation) of genetic material between chromosome 9 and chromosome 22. This translocation, written as t(9;22), fuses part of the ABL1 gene from chromosome 9 with part of the BCR gene from chromosome 22, creating an abnormal fusion gene called BCR-ABL1. The abnormal chromosome 22, containing a piece of chromosome 9 and the fusion gene is often referred to as the Philadelphia chromosome (named for where it was first discovered). The translocation is acquired during a person's lifetime and is present only in abnormal blood cells. This type of genetic change, called a somatic mutation, is not inherited.

The function of the protein produced from the normal BCR gene is not completely understood, although it has been shown to help control signaling in cells. The protein produced from the normal ABL1 gene is involved in many cellular processes, including cell growth and division (proliferation), maturation (differentiation), movement (migration), and self-destruction (apoptosis).

Like the ABL1 protein, the abnormal protein produced from the fusion gene, called BCR-ABL1, can promote cell proliferation and block apoptosis. However, unlike ABL1, it does not require signals in the cell to turn it on. The constantly active BCR-ABL1 protein signals cells to continue dividing abnormally and prevents them from self-destructing, which leads to overproduction of the abnormal cells and, eventually, a shortage of normal blood cells. The presence of the Philadelphia chromosome provides a target for molecular therapies in people with chronic myeloid leukemia.

In 5 to 10 percent of cases of chronic myeloid leukemia, the BCR-ABL1 fusion gene is created by complex rearrangements that involve other chromosomes in addition to chromosomes 9 and 22. These genetic changes are called variant Philadelphia translocations. These cases are similar to those caused by t(9;22).

Researchers believe that additional genetic changes play a role in the progression of the chronic phase of chronic myeloid leukemia to the accelerated phase and blast crisis. The most common genetic changes associated with progression to blast crisis include an extra copy of chromosome 8 (trisomy 8), an abnormality of chromosome 17 known as isochromosome 17, and an extra copy (duplication) of the Philadelphia chromosome. When these somatic mutations occur in cells with the Philadelphia chromosome, they likely further promote uncontrolled cell proliferation.

Inheritance described in the linked summary

From: MedlinePlus Genetics

This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation.

Which doctor should you see?

The suggested department for discussing Chronic Myeloid Leukemia is Oncology, with a oncologist and relevant organ specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics; Relevant organ specialist / Surgical Oncology as indicated.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Has the exact tumour type been confirmed, and is staging relevant?
• What is the goal of each proposed treatment option?
• How will side effects, daily function and supportive care be addressed?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.