Chronic Myeloid Leukaemia: Symptoms, Causes & Treatment

Chronic Myeloid Leukaemia

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Chronic myeloid leukaemia, also known as chronic myelogenous leukaemia, is a rare form of cancer in the bone marrow or the spongy tissue inside bones where blood cells are generated. In CML, there is a subsequent rise in the white blood cell count. The word "chronic" in chronic myelogenous leukaemia denotes that this malignancy tends to advance more slowly than acute leukaemia. 

Therapy advancements have achieved a significantly better prognosis for those with chronic myeloid leukaemia symptoms. After diagnosis, most patients will have remission and live a long time. In this article, we will discuss all CML, its symptoms, types, causes, diagnosis, prevention, medicine, treatment and other essential details.

Disease Name

Chronic Myeloid Leukaemia

Alternative Name

Chronic Myelogenous Leukaemia

Symptoms

Weakness, Tiredness, Shortness of breath, Night sweats, Bone pain, Weight loss

Causes

Genetics, Age, Family history, Chemical exposure, Environmental factors

Diagnosis

Blood tests, Bone marrow biopsy, 

Treated by

Medical Oncologist, Surgical Oncologist

Treatment Options

Chemotherapy, Targeted Therapy, Immunotherapy, Stem cell transplant

What is Chronic Myeloid Leukaemia?

Chronic myeloid leukaemia is a type of blood cancer that begins in the bone marrow's myeloid cells or stem cells. Other names for the illness include chronic granulocytic leukaemia and chronic myelogenous leukaemia. 

  1. A genetic alteration (mutation) in the bone marrow-produced stem cells leads to CML. The mutation makes the stem cells create an excessive number of immature white blood cells. 

  2. Additionally, it causes a decline in the number of other blood cells, like red blood cells and chromosomes, or collections of DNA, which may be altered.

  3. Here a piece of DNA from one chromosome switches places with a piece from another within each stem cell. 

The "Philadelphia chromosome" is the name given to this mutation. Although the exact cause of this is unknown, it cannot be passed down to the offspring (child) and is not a trait that one is born with.

Now, many CML patients are leading a normal life, all thanks to therapy, which has transformed the condition from a life-threatening sickness.

Chronic Myeloid Leukaemia Stages

About 15% of all leukaemia patients suffer mainly from chronic myeloid leukaemia. CML can strike anyone at any age. However, it usually strikes elderly people.  

There are four chronic myeloid leukaemia stages:

  1. Chronic CML: The word "chronic" frequently denotes a persistent condition. This phrase CML refers to the proportion of blasts (immature white blood cells) in the bone marrow and blood. 

    1. When suffering from chronic CML, about 10% of the blood and bone marrow cells are blasted. For about 80% to 90% of cases, CML is chronic for most patients. However, patients suffering from chronic CML may or may not experience symptoms.

  2. Accelerated CML: In this stage, blasts comprise 10% to 19% of the blood or bone marrow cells. Basophils are white blood cells that secrete enzymes to enhance blood flow and avoid blood clots. One might have higher basophil levels if he/she has CML.

  3. Blast (Blast Crisis) CML: Blast CML is life-threatening. Tests have shown that blasts make up 20% or more cells in the blood or bone marrow. People with blast phase CML have prominent symptoms like fatigue, fever, weight loss and shortness of breath. 

  4. Resistant CML: Resistant CML is a condition that recurs after therapy or doesn't improve the patient’s condition.

Chronic Myeloid Leukaemia Symptoms

Different phases of CML may have different symptoms. A person might not have any symptoms throughout the chronic stage. But, when they show up, they are non-specific, which means they may resemble the symptoms of numerous other illnesses. 

The significant chronic myeloid leukaemia symptoms include: 

  1. Weakness

  2. Tiredness

  3. Shortness of breath

  4. Night sweats

  5. Bone pain

  6. Weight loss

  7. Fever

  8. Feeling bloating in the stomach

  9. Feeling full after very easily

  10. Tenderness in the left side of the stomach

  11. Pale skin and shortness of breath

  12. A high temperature

  13. Bruising and bleeding easily

  14. Frequent infections

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Chronic Myeloid Leukaemia Cause

The exact cause of CML is not well understood, but researchers believe that a combination of genetic and environmental factors plays a role in its development.

Chronic Myeloid Leukaemia Risk Factors

The risk factors that increase an individual's likelihood of developing CML are as follows. 

  1. Older Age: The risk of getting CML goes up with age. The average age of those who receive a CML diagnosis is 64.

  2. Gender: It is unknown why men are significantly more likely than women to have this condition.

  3. Exposure to Radiation: The risk of developing CML rises with high-dose radiation exposure (such as being a survivor of an atomic bomb explosion or nuclear reactor accident). 

  4. Family History: While most CML cases are not inherited, having a family member with CML or another type of leukaemia may slightly increase the risk of developing the disease.

  5. Previous Cancer Treatments: Individuals who have received certain types of chemotherapy or radiation therapy for other cancers may have a slightly higher risk of developing CML later in life. However, the absolute risk remains relatively low.

Prevention of Chronic Myeloid Leukaemia

It is believed that mutations are to be blamed for the progression of CML. Therefore, there are no known preventive measures that can guarantee the avoidance of CML.

However, it is important to focus on overall health and well-being, as maintaining a healthy lifestyle may positively impact overall cancer risk. Here are some general recommendations for maintaining good health:

  1. Regular Check-ups: Regular visits to healthcare providers can help detect any health issues early on and allow for prompt intervention if necessary.

  2. Healthy Diet: Eating a balanced diet that includes a variety of fruits, vegetables, whole grains, lean proteins, and healthy fats is important for overall health. While it may not prevent CML, a nutritious diet can support a strong immune system and help maintain overall well-being.

  3. Physical Activity: Engaging in regular physical activity, such as walking, swimming, or cycling, can help maintain a healthy weight, improve cardiovascular health, and boost overall well-being.

  4. Avoiding Exposure to Radiation and Harmful Chemicals: Minimizing exposure to unnecessary radiation and harmful chemicals, such as certain industrial chemicals or pesticides, may reduce the risk of developing certain cancers, although the specific link to CML is not established.

  5. Smoking and Alcohol: Avoiding tobacco use and limiting alcohol consumption can reduce the risk of various types of cancer, including some forms of leukaemia. Quitting smoking and seeking help for alcohol dependency are important steps towards better health.

How is Chronic Myeloid Leukaemia Diagnosed?

Chronic Myeloid Leukemia (CML) is typically diagnosed through a combination of medical history evaluation, physical examination, blood tests, and bone marrow tests. Chronic myeloid leukaemia pathology outlines include:

  1. Physical Exam: The doctor will examine and measure the blood pressure and pulse, among other vital indicators. To evaluate whether the lymph nodes, spleen, or belly are swollen, he or she will also examine these parts.

  2. Complete Blood Count (CBC): This test will measure the number of different types of blood cells. In CML, an elevated white blood cell count, specifically an increased number of immature white blood cells called blasts, may indicate the presence of the disease. 

    1. The blood tests may also include a peripheral blood smear to examine the appearance of the blood cells under a microscope.

  3. Bone Marrow Aspiration or Biopsy: Pathologists take small fluid or tissue samples for genetic tests. They would then perform tests to analyse abnormal cells’ genetic makeup.

  4. Genetic Tests: To determine if the Philadelphia chromosome or the BCR-ABL gene is present in blood or bone marrow samples, specialised techniques like the fluorescence in situ hybridisation (FISH) analysis and the polymerase chain reaction (PCR) test are used.

  5. Computed Tomography (CT) Scan: This test is used to determine the effect of CML in another body part.

  6. Ultrasound: Medical professionals may use this test to assess whether the spleen is larger than usual. One significant symptom of CML is an enlarged spleen.

How to Prepare for Doctor’s Consultation?

The first step towards diagnosing CML is the doctor checking the patient's overall health and the normal functioning of their vital organs.

There are some things that the patient must keep in mind to prepare for the doctor’s consultation appointment. These include:

  1. Taking a prior appointment

  2. Enlisting symptoms

  3. Writing down personal information, including medical history

  4. Making a list of questions for the doctor

What to Expect from the Doctor?

The doctor will ask the person some questions that will allow them a proper diagnosis of the problem. Some of the most common questions include: 

  1. The duration for which a person has been experiencing the symptoms

  2. The frequency and severity of the symptoms 

  3. Things that provide relief in the symptoms

  4. Things that worsen the symptoms 

Questions the Patient Can Ask?

These are some of the questions that one should ask their doctor.

  1. What phase am I in with chronic myeloid leukaemia?

  2. What alternatives do I have for treatment?

  3. How will my medical therapy feel?

  4. Can I go to work while receiving treatment?

  5. How frequently will blood tests be conducted to monitor my treatment's effectiveness?

  6. What are the possibilities that CML will remit?

  7. In my situation, would a stem cell transplant be beneficial?

  8. Who can I contact regarding controlling my medical expenses?

Chronic Myeloid Leukaemia Treatment

Treatment for chronic myelogenous leukaemia aims to eradicate blood cells that carry the faulty BCR-ABL gene, which is the source of the excess number of diseased blood cells. Most patients start their course of treatment with certain medications that could lead to a long-term remission of their illness.

  1. Chemotherapy: Chemotherapy is a medication therapy that destroys the body's rapidly proliferating cells, including leukaemia cells. When treating aggressive, chronic myelogenous leukaemia, chemotherapy medications are occasionally coupled with targeted pharmacological therapy. Depending on the medication that the patient is taking, chemotherapy medications can have side effects.

  2. Targeted Drug Therapy: To combat cancer, targeted medications target a particular kind of cancer cells that promotes their growth and multiplication. These medications target tyrosine kinase, a protein made by the BCR-ABL gene, in chronic myelogenous leukaemia. Chronic myeloid leukaemia medicine that prevents tyrosine kinase activity includes:

    1. Imatinib (Gleevec)

    2. Dasatinib (Sprycel)

    3. Nilotinib (Tasigna)

    4. Bosutinib (Bosulif)

    5. Ponatinib (Iclusig)

  3. Bone Marrow Transplant: The only option for permanent recovery from chronic myelogenous leukaemia is a bone marrow transplant, commonly known as a stem cell transplant. However, because bone marrow transplants are risky and have a high probability of significant consequences, they are often only used for patients who haven't responded to previous treatments. 

  4. Clinical Trials: Clinical trials investigate innovative methods of administering existing medications or the most recent illness treatments. Even though participating in a clinical trial for chronic myelogenous leukaemia may allow one to try the newest medication, it cannot promise a cure. 

  5. Supportive Care: Alongside the main treatment approaches, supportive care plays a crucial role in managing CML treatment's side effects and complications. Supportive care may include medications to manage symptoms like nausea, pain, or infections and blood transfusions to address anaemia or platelet deficiencies.

Cost of Chronic Myeloid Leukaemia Treatment

The cost of CML treatment in India depends on several factors, including the stage of cancer, treatment modality used, patient’s age, patient’s comorbidities, hospital type and location, doctor’s experience, insurance coverage and much more.

To know the exact cost of CML treatment in India, one must visit their doctor, or the below table provides the approximate cost of various treatment modalities for CML.

Surgery Name

Surgery Cost

Chemotherapy

₹ 75,000 to ₹ 2,50,000

Targeted Therapy

₹ 80,000 to ₹ 2,25,000

Bone Marrow Transplant

₹ 15,00,000 to ₹27,00,000

Chronic Myeloid Leukaemia Survival Rate

The survival rate for CML has significantly improved over the past few decades due to advancements in treatment options. However, it's important to note that survival rates can vary based on several factors, including the phase of the disease, age of the patient, response to treatment, and overall health. 

The five-year survival rate represents the percentage of people who are alive five years after their diagnosis. For CML, the overall five-year survival rate is estimated to be 90%. Only 22% of CML patients were alive five years before TKI. The best source of information about what to anticipate if one has CML is the doctor who treats him/her.

Risks and Complications of Chronic Myeloid Leukaemia

Chronic Myeloid Leukemia (CML) is a type of cancer that can lead to various risks and complications if not properly managed. Here are some of the risks and complications associated with CML:

  1. Hepatomegaly and/or Splenomegaly: Splenomegaly is another name for an enlarged spleen. It is a sign of the underlying condition, which is the CML. Splenomegaly is brought on by benign or malignant growths as well as an excessive generation of cells.

  2. Worsening Anaemia: Anaemia is frequently present in chronic phase chronic myeloid leukaemia (CML-CP) patients at diagnosis, but it is unclear how this affects the prognosis. Patients with moderate anaemia have more aggressive characteristics, such as higher WBC counts and greater percentages of myeloblasts and basophils, compared to those with non-moderate anaemia, including a higher proportion of intermediate-high Sokal hazards. 

  3. Clotting or Bleeding Complications: There may be a change in the platelet count due to CML, which can further lead to clotting and bleeding complications.

  4. Recurrent Infections: An increased risk of viral infections, particularly the reactivation of latent viruses like varicella zoster and hepatitis B, exists in patients diagnosed with CML. As evidenced by the large number of patients who experience viral reactivation in the chronic phase, this is probably due to the disease.

  5. Fatigue: There is a serious loss of energy that cannot be remedied by sleep. It can be difficult to participate in daily activities if a patient has CML fatigue because it doesn't get better or go away with time. 

Risk of Delayed Treatment

Delaying the diagnosis and treatment of CML can have serious consequences for the patient's health. To attain the best results, treatment must begin right away after a diagnosis. The following are potential dangers of delaying CML treatment:

  1. The illness can advance quickly, increasing the number of cancer cells in the bone marrow and blood. As a result, there may be a greater burden of leukaemia cells present throughout the body and more extensive organ involvement.

  2. Delaying treatment may make CML symptoms, including fatigue, weakness, unexplained weight loss, abdominal discomfort, and an enlarged spleen, worse or continue to exist. 

  3. Untreated or undertreated CML can lead to serious complications

  4. Delaying treatment can raise the possibility that CML will develop into an acute leukaemia-like condition that is more aggressive and challenging to treat. This change is frequently linked to worse outcomes and few available treatments.

When to See a Doctor?

It is important to consult a doctor if one experiences any concerning symptoms or risk factors associated with CML Here are some situations when one should seek medical attention:

  1. Persistent fatigue

  2. Unexplained weight loss

  3. Abdominal discomfort

  4. Unusual sweating

  5. Bruising and bleeding

  6. Recurrent infections

Diet for Chronic Myeloid Leukaemia

Eating habits often change for most patients when receiving cancer therapy. It has been noticed that radiation has the potential to cause excessive weight loss, lean body mass loss, and malnutrition. To maintain weight, it's necessary to make an effort to consume enough protein, carbohydrates, and fats. 

A healthy diet that includes food items rich in nutrition, minerals, and lots of water to stay hydrated might also help the patient maintain their weight. The Leukaemia and Lymphoma Society (LLS) provides the following general dietary recommendations:

  1. A variety of vegetables, including legumes

  2. Whole fruits

  3. Whole grains

  4. Fat-free or low-fat dairy

  5. Food rich in proteins

  6. Seafood, lean meats, poultry, beans, soy, and eggs

  7. Healthy oils, such as olive oil

  8. Water, tea, or coffee for hydration

Takeaway

Chronic myeloid leukaemia (CML) is frequently known as cancer of the blood and bone marrow. Receiving treatment when suffering from the early, chronic stage of CML can help stop the condition from progressing to a more serious stage.

You should consult a haematologist-oncologist as soon as you are diagnosed. They'll develop a therapy strategy for you, with the treatment's objective being to eliminate the leukaemia blood cells from your body and replenish healthy blood cells to a normal level. 

So, reach out to HexaHealth to know about the newer therapies or clinical trials that could allow you to be CML-free if you have the disease. Also, via HexaHealth, you would connect with the best oncologists to battle chronic myeloid leukaemia.

Suggested Reads

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Leukaemia vs Lymphoma
Acute Myeloid Leukaemia
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FAQs for Chronic Myeloid Leukaemia

According to chronic myeloid leukaemia definition, it is a rare form of cancer in the bone marrow or the spongy tissue inside bones where blood cells are generated.

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The chronic myeloid leukaemia symptoms include –

  1. Weakness

  2. Bone pain

  3. Weight loss

  4. Fever

  5. Feeling bloating in the stomach

  6. Bruising and bleeding easily

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There are four chronic myeloid leukaemia stages-

  1. Chronic CML 

  2. Accelerated CML 

  3. Blast (blast crisis) CML

  4. Resistant CML

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The following tests are used to identify chronic myelogenous leukaemia:

  1. Physical exam. 

  2. Blood tests. 

  3. Bone marrow tests. 

  4. Tests to look for the Philadelphia chromosome. 

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The available chronic myeloid leukaemia treatment options are as follows-

  1. Targeted drug therapy

  2. Bone marrow transplant

  3. Chemotherapy

  4. Clinical trials

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A genetic alteration (mutation) in the bone marrow-produced stem cells leads to CML. There are several things that raise the risk of developing chronic myelogenous leukaemia.

  1. Old age: Compared to teens and children, elderly persons have a greater risk of CML.

  2. Being a male: Men are somewhat more likely than women to develop CML.

  3. Radiation exposure: Developing CML has been associated with radiation therapy for certain types of cancer.

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The only method available to "cure" chronic myeloid leukaemia is allogeneic stem cell transplantation. Donated stem cells are used in allogeneic stem cell transplants. It's a challenging medical procedure.

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Initially, it was believed that mutations were to blame for the progression of chronic myeloid leukaemia (CML). However, the same thing might be caused by changed DNA methylation. It is believed that an appropriate pyridoxine analogue could stop CML from progressing by obstructing DNA methylation.

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The pathological feature of chronic myelogenous leukaemia (CML) is the presence of a significant number of immature white blood cells from the myelogenous series in blood known as myelocytes, in the blood. 

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While explaining acute myeloid leukaemia vs chronic myeloid leukaemia, we may say that Chronic leukaemia grows slowly and the cells partially mature, whereas acute leukaemia grows quickly and swiftly in the absence of treatment. The optimum effect can be achieved by starting treatment as soon as feasible.

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BCR-ABL1-positive chronic myeloid leukaemia (CML) is categorised as a myeloproliferative neoplasm and has been found to have the translocation t(9;22)(q34;q11.2) on the Philadelphia chromosome.

Peripheral blood and bone marrow are both impacted by CML. Involved cell lineages include megakaryocytes, erythroid precursors, resident macrophages, and lymphocytes in addition to neutrophil granulopoiesis, to varying degrees.

Furthermore, the stromal compartment—particularly the collagen and reticulin fibres—plays a crucial function in the development of the disease.

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The primary medication used to treat CML is a drug called imatinib. It is typically administered quickly after a cancer diagnosis in order to decrease the disease's course and keep it from progressing to an advanced stage.

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It takes a long time for CML to get worse. You can have this condition for years before noticing symptoms. There are four chronic myeloid leukaemia stages-

  1. Chronic CML 

  2. Accelerated CML 

  3. Blast (blast crisis) CML

  4. Resistant CML

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The CML blast crisis phase resembles acute leukaemia, particularly the severe form of acute leukaemia in the blast crisis known as B-cell acute lymphoblastic leukaemia (B-ALL) for which there is now no viable treatment.

The BCR-ABL oncogene, whose gene product is a BCR-ABL tyrosine kinase, causes CML.

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Epidemiological studies have shown that, in addition to chromosomal abnormalities, a number of other factors, such as ionising radiation exposure, personal and family medical histories, exposure to chemical or biological agents, such as solvents and benzene, smoking habits, and lifestyle factors, are related to the incidence of CML and acute lymphoid leukaemia.

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In the UK, a number of clinical trials are going on to find the treatment of leukaemia. Clinical trials is a form of study that uses new and experimental techniques to see how well they work in curing diseases.

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Around 70 percent of men and 75% of women are predicted to survive for at least 5 years following their diagnosis.

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Chromosome abnormalities and widespread changed genes are two genetic abnormalities that have been linked to CML in the blast phase. Some of these genes, such the epidermal growth factor receptor (EGFR), tumour protein p53 (TP53), or Schmidt-Ruppin A-2 proto-oncogene (SRC), are involved in the control of cell apoptosis and proliferation.

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Complications of CML can include:

  1. Hepatomegaly and/or splenomegaly

  2. Worsening anaemia

  3. Changes in platelet count changes resulting in clotting or bleeding complications

  4. Recurrent infections

  5. Bone pain

  6. Fever

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A support network called CML Connection organises meetings all across the country for individuals with chronic myeloid leukaemia and their families. All CML patients, as well as their loved ones and carers, are welcome to the support groups.

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The following list of studies is gradually being made to improve the efficacy of CML treatments:

  1. Combining imatinib with other medications

  2. Developing BCR-ABL vaccines

  3. Creating novel techniques for bone marrow/stem cell transplantation with the goal of reducing negative effects

  4. Examining different novel TKIs for CML that are not responsive to imatinib

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The ability to receive therapy may be hampered by false beliefs regarding chronic myeloid leukaemia (CML). Here are some of the myths you might hear that are associated with CML –

  1. Myth: CML has clear and specific symptoms.
    Fact: CML is discovered in about half of people who are asymptomatic after a normal full blood count. The majority of people have CML symptoms at its chronic stage. The symptoms of anaemia and splenomegaly are the ones that CML patients commonly exhibit most frequently when it is in the chronic phase. Fatigue and malaise are examples of symptoms of symptomatic anaemia.

  1. Myth: CML can’t be treated.
    Fact: There are a number of treatment options for treating CML. However, currently, the only method available to "cure" chronic myeloid leukaemia is allogeneic stem cell transplantation.

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References

All the articles on HexaHealth are supported by verified medically-recognized sources such as; peer-reviewed academic research papers, research institutions, and medical journals. Our medical reviewers also check references of the articles to prioritize accuracy and relevance. Refer to our detailed editorial policy for more information.


  1. Mayo Clinic. Chronic myelogenous leukemia - Symptoms and causes [Internet]. Mayo Clinic. 2019. link
  2. Chronic Myelogenous Leukemia (CML): Symptoms, Treatment & Survival Rate [Internet]. Cleveland Clinic. link
  3. Chronic Myeloid Leukemia (CML): Diet and Nutrition Tips [Internet]. Healthline. 2022. link
  4. Sastry PSRK. Prevention of progression in chronic myeloid leukemia by altering DNA methylation with a pyridoxine analogue. Medical Hypotheses. 1999 Dec;53(6):488–9.link
  5. Chronic myelogenous leukemia | pathology | Britannica [Internet]. www.britannica.com. [cited 2023 Jun 29].link
  6. Chronic myeloid leukaemia - Treatment [Internet]. nhs.uk. 2017.link
  7. Chen Y, Peng C, Li D, Li S. Molecular and cellular bases of chronic myeloid leukemia. Protein & Cell [Internet]. 2010 Feb 1 [cited 2020 Feb 17];1(2):124–32. link
  8. Maleki Behzad M, Abbasi M, Oliaei I, Ghorbani Gholiabad S, Rafieemehr H. Effects of Lifestyle and Environmental Factors on the Risk of Acute Myeloid Leukemia: Result of a Hospital-based Case-Control Study. Journal of Research in Health Sciences. 2021 Aug 12;21(3):e00525–5.link
  9. Leukemia - Chronic Myeloid - CML - Latest Research [Internet]. Cancer.net. 2012.link
  10. Eden RE, Coviello JM. Chronic Myelogenous Leukemia [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Jun 29]. link
Disclaimer: The information provided here is for educational and learning purposes only. It doesn't cover every medical condition and might not be relevant to your personal situation. This information isn't medical advice, isn't meant for diagnosing any condition, and shouldn't replace talking to a certified medical or healthcare professional.

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