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Chronic Myelogenous Leukemia (CML)

What is chronic myelogenous leukemia?

The bone marrow plays a pivotal role in the production of blood cells for the body’s ability to defend itself. In a healthy individual, the bone marrow generates stem cells, which subsequently mature into white blood cells, red blood cells or platelets that circulate throughout the bloodstream. Leukemia develops due to abnormalities in these stem cells, resulting in the unregulated proliferation of white blood cells that circulate in the bloodstream.

Chronic myeloid leukemia (CML), also known as chronic granulocytic leukemia or chronic myelogenous leukemia is an uncommon type of cancer in the bone marrow. This type of leukemia can affect almost anyone but is most commonly found in middle aged adults and affects the white blood cells called myeloid cells. The overproduction of immature myeloid cells, which are known as blasts, prevents the bone marrow from producing healthy blood cells of all types.

Myeloid cells, a category of white blood cells, include granulocytes, monocytes, macrophages and dendritic cells, any of which have the potential to lead to the development of chronic myeloid leukemia when found in abnormal amounts.

Chronic Myelogenous Leukemia (CML) - Adults

Other Types of Leukemia

Leukemias are categorized based on whether they affect myeloid or lymphoid white blood cells, leading to myelogenous or lymphocytic classifications, respectively.

Chronic myeloid leukemia (CML) is a cancer of the blood with an accumulation of white blood cells called granulocytes that are produced in the bone marrow and whose main responsibility is to kill bacteria. Unlike acute myeloid leukemia (AML), CML progresses slowly over time, while acute leukemia rapidly progresses. CML in the blast phase can develop into AML, leaving patients vulnerable to infections and a quicker onset of symptoms than CML patients due to AML’s accelerated progression rate. AML affects the overproduction of immature white blood cells known as the myeloblasts, which are prevented from maturing into functioning blood cells, outnumbering the healthy cells. AML can spread to the brain, spinal cord, liver and spleen – and without proper intervention, AML can be life threatening.

Chronic lymphocytic leukemia (CLL) is a form of blood cancer characterized by an excess of lymphocytes originating from the bone marrow and lymphatic organs with a slow but gradual progression rate. Predominantly affecting adult males over the age of 70 with minimal or even no symptoms, years can go by before patients require any medical intervention. Patients with CLL may experience persistent weakness (fatigue), coughing, bowel inconsistencies, loss of appetite (due to an enlarged spleen), recurring infections and easily bruising and bleeding.

Acute lymphocytic leukemia (ALL) describes a major and very rapid proliferation of immature lymphocytes called lymphoblasts, a type of white blood cell produced in the bone marrow and the lymphatic system. Symptoms include frequent infections, bleeding or bruising easily, constant fatigue and dramatic weight loss. Those affected with ALL may have a family history of ALL, may suffer from genetic disorders such as Down syndrome, may have received chemotherapy or radiation therapy in the past or previously had certain viral infections such as human T-cell lymphoma.

Types of CML

The term “chronic” in CML describes a slow growing cancer, though it can transform into AML or acute myeloid leukemia, which grows quite rapidly and requires immediate medical attention.

CML can be divided into three types or phases – chronic, accelerated and blast phase. People often find out that they have CML after a routine blood test that comes back with an irregular blood count, which is the chronic phase. This phase generally does not present with many symptoms, if at all, and can be controlled with drugs. If at any time a patient develops drug resistance, the disease may progress into the accelerated phase.

The accelerated or blast phase of the disease presents a far greater number of immature blood cells than that of the chronic phase as well as more symptoms. The accelerated phase presents with an enlarged spleen, low red blood cell count and an increase or decrease in white blood cells.

The blast phase of CML puts patients at a very high risk for other complications such as shortness of breath, infection and bleeding. Once CML goes into the blast phase, it can shift into acute myeloid leukemia and requires immediate medical intervention.

Unfortunately, CML can include a relapse phase, where you may have gone into complete remission, only to find that your blood tests came back abnormal and the blasts started to proliferate yet again. This can happen when certain patients become drug resistant due to the BCR-ABL1 gene mutation. Regarding treatment options for relapsed patients, the goal is to revert them back to the chronic phase and this is often done with targeted therapy using a tyrosine kinase inhibitor.

CML Causes

Chronic myeloid leukemia is caused by a sudden genetic mutation in the stem cells of the bone marrow, causing an overproduction of immature white blood cells while lowering the healthy cell count.

CML is characterized by the presence of the Philadelphia chromosome. Each cell in the body contains DNA, which serves as the genetic material that determines and defines the functions of these cells. In the case of CML, a unique scenario unfolds where specific segments of chromosome 9 and chromosome 22 undergo a reciprocal translocation, resulting in an elongated chromosome 9 and a shortened chromosome 22, i.e., the Philadelphia chromosome.

This alteration in chromosome structure and positioning leads to the formation of a novel gene called BCR-ABL, resulting in a newly synthesized protein known as tyrosine kinase. Tyrosine kinase, in turn, triggers uncontrolled proliferation of white blood cells, leading to an excessive accumulation of diseased and dysfunctional white blood cells, which outnumber their healthy counterparts.

CML Risk Factors

Risk factors are anything that can increase the likelihood of a person to develop cancer but usually do not cause cancer. It is possible to have no known risk factors and still develop cancer. Knowing about the risks and discussing them with your doctor can help you control and mitigate your health as best as you possibly can. The main risk factors associated with CML include:
  • Age: The average age a person can be diagnosed with CML is around 64. This cancer is very uncommon among children and teens.
  • Radiation exposure: Many people who were around the 1945 atomic bombings in Japan were diagnosed with CML. Additionally, a condition known as ankylosing spondylitis often treated with radiation therapy has been linked with CML. Otherwise, there are no known links to CML caused by radiation or chemotherapy.
  • Gender: Men are more likely to develop CML than women.
  • The Philadelphia Chromosome: Nearly all CML patients have the Philadelphia chromosome which develops after birth and can be detected only with a specific test for this genetic abnormality.

CML Symptoms

As frightening as it may sound, it could take years before CML can fully develop to the point where it can interfere with your life and may be discovered after a routine physical examination or blood test. Chronic myeloid leukemia symptoms include:
  • Fatigue
  • Shortness of breath during normal physical activity
  • Dull or pale skin
  • Feeling full or discomfort in left upper abdomen due to an enlarged spleen
  • Drenching night sweats
  • Fever
  • Unexplained and dramatic weight loss
  • Bone pain
  • Loss of appetite
  • Bleeding easily

Potential Complications of CML

People with CML may develop anemia due to a lack of red blood cells and an enlarged spleen, a common symptom for CML. 30% of people diagnosed with CML may also encounter secondary cancers such as small bowel, thyroid, stomach, lung and prostate cancer.

CML Diagnosis

It is important to note that most people with CML have no onset of symptoms when diagnosed. It is very possible to go to the doctors for a completely unrelated blood test or an unrelated health problem and discover that your white blood cell count is abnormal which may lead your doctor to suspect CML. To officially diagnose for CML, doctors use a variety of tests to analyze your blood and bone marrow cells. The samples gathered from these tests will be observed by a pathologist and hematopathologist who specializes in diseases of the blood and bone marrow. These tests include:
  • Complete blood count (CBC) with differential: This test will provide current red blood cell counts, white blood cell counts, platelet counts and hemoglobin levels within red blood cells. The differential analysis will specifically categorize the various types of white blood cells. People with CML often have a dramatically high white blood cell count, a decreased red blood cell count and either an increase or decrease in the platelet count (depending on the severity of their CML).
  • Peripheral blood smear: This is a technique doctors use to examine your red and white blood cells as well as your platelets to provide status of health of your blood.
  • Bone marrow aspiration and biopsy: The doctor will collect and examine bone marrow to see whether your bone marrow is healthy and functioning properly or not.
  • Cytogenetic analysis: Special stains are applied to the bone marrow and then the cells are observed to detect any abnormalities in chromosomal structure, such as the Philadelphia chromosome.
  • Fluorescence in situ hybridization (FISH): Laboratory test used to examine genes and chromosomes in cells and much more effective diagnostic method than cytogenetic testing.
  • Quantitative polymerase chain reaction (qPCR): The most sensitive test used to detect and measure the quantity of BCR:ABL1 gene in blood or bone marrow samples.

Treatment Options for CML

The esteemed team of specialists at Sheba utilize cutting-edge technology to seamlessly integrate and thoroughly evaluate all test results for quick and accurate diagnosis and treatment. Your treatment options will depend on the type of leukemia you have as well as the current stage of progression. These factors will indicate which of the following your healthcare team will recommend as your treatment plan:
  • Chemotherapy: Interferes with the leukemia cells ability to multiply and grow.
  • Targeted therapy: This utilizes drugs and other substances that are able to recognize and attack cancer cells without harming healthy cells.
  • Radiation therapy: This therapy is most commonly used in which high-energy rays are used to damage or even kill cancer cells and shrink tumors.
  • Bone marrow transplant: This is often recommended after a patient with a damaged bone marrow. Once the patient enters remission, they are given new bone marrow from a donor.
  • CAR-T cell therapy (patients with ALL): This is an innovative form of immunotherapy where a patient’s T-cells are reprogrammed at Sheba’s in-house lab and then transplanted back into the patient to target the cancer cells.
Beyond drug intervention, Sheba cannot stress enough the level of importance when it comes to the patient’s quality of life. Your healthcare team does not only include oncologists and hematologists but also a team of social workers, nutritionists as well as alternative therapy practitioners. Sheba’s dedicated team of experts will guide you through the entire process and keep you informed of all the various testing and therapies available to you and what to expect.

Living with CML

Unlike some cancers, chronic leukemia often doesn’t manifest noticeable physical symptoms, allowing those around you to remain unaware of your condition. Receiving a chronic myeloid leukemia diagnosis can indeed be an overwhelming experience. In cases where the CML diagnosis is categorized as low risk, and your doctor assures you that it should not disrupt your daily life, it can become more challenging to seek support or confide in loved ones due to concerns about burdening them with your struggles.

A favorable prognosis doesn’t necessarily translate to an easy journey when dealing with conditions like chronic myeloid leukemia. Chronic cancers, including CML, become a lasting part of your life, distinguishing them from other types of cancer that may resolve after treatment. While some individuals may eventually discontinue treatment, many continue to require ongoing medical care and monitoring, without a definite endpoint in sight. Consequently, planning for life beyond cancer can be challenging, as it can be difficult to adapt to this long-term reality. Nonetheless, you shouldn’t navigate this difficult journey on your own.

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