Some non-inherited genetic abnormalities put people at risk for certain diseases, including chronic myeloid leukemia, a type of blood cancer. However, people may not realize that they have the condition, because half of people who are diagnosed don’t experience any symptoms, and doctors don’t look for the mutation unless they suspect the disease.  

Roughly 9,000 people are diagnosed with chronic myeloid leukemia (CML) every year in the United States. This type of cancer affects males more frequently than females, and accounts for about 15% of all adult leukemia cases in the U.S.  

People are commonly diagnosed when they are age 65 or older; it’s uncommon for children and teens to develop this form of cancer.  

Advances in treatment—including targeted therapy—over the past few decades have helped many people survive chronic myeloid leukemia.  

“The treatment of CML was revolutionized 20 years ago and serves as an example as one of the most critical milestones in translating an understanding of cancer biology into targeted treatment, which offers most patients a ‘functional cure,’” says Smilow Cancer Hospital hematologist Rory Shallis, MD. “These oral therapies come in several forms, each with differing side effect profiles and subtle differences in indication that make the specific choice of agent personalized to the individual patient. Although the vast majority of patients with CML will fare remarkably well with these effective therapies, clinical trials are ongoing to move the needle further, and some patients even require consideration for a bone marrow transplant.”

Chronic myeloid leukemia is a type of blood cancer that causes a types of white blood cell, called a granulocyte, to reproduce uncontrollably.

Myeloid cells are located within the bone marrow. In healthy people, myeloid cells produce red blood cells, platelets, and some (but not all) white blood cells. Sometimes, immature myeloid cells experience a genetic abnormality known as BCR-ABL. When this occurs, they produce uncontrolled numbers of granulocytes. These white blood cells may look normal, but they don’t function properly, so they don’t fight disease or protect the immune system as they normally would. The proliferation of these white blood cells throws off the proportion of red blood cells, white blood cells, and platelets. Eventually, the abnormal white blood cells leave the bone marrow and enter the bloodstream and spread to other parts of the body.

A genetic abnormality that occurs during a person’s lifetime (rather than one that has been inherited from a parent) causes chronic myeloid leukemia. It’s not possible to pass this abnormality along to children.

Normally, when cells divide, the DNA within the cells copies itself accurately, and no abnormalities occur. However, when a person develops chronic myeloid leukemia, two chromosomes—chromosome 9 and chromosome 22—swap some of their genetic information with each other during division of blood-forming cells. When chromosome 22 mutates this way, it’s known as a Philadelphia chromosome. Its presence confirms chronic myeloid leukemia.

When chromosomes 9 and 22 exchange genetic material, it leads to the creation of a new gene, called BCR-ABL. This gene produces a tyrosine kinase protein that promotes uncontrolled growth of the granulocytes.

About half of people with chronic myeloid leukemia don’t experience any discomfort or other symptoms. They don’t know that they have the condition until the discovery is made during routine bloodwork.

Other people with this type of cancer may experience:

• Fatigue
• Unexpected weight loss
• Night sweats
• Fever
• Enlarged spleen
• Pain beneath the rib cage on the left side of the body
• A feeling of fullness beneath the rib cage on the left side of the body
• Bleeding
• Bone pain
• Anemia
• Unexplained bruises
• Skin rashes

Doctors may discover chronic myeloid leukemia after ordering routine bloodwork for patients who appear healthy. Other times, if a patient visits the doctor with concerns about their health, doctors may diagnose the condition after learning about the patient’s health history, performing a physical, and ordering diagnostic tests.

There are few risk factors for chronic myeloid leukemia, so doctors may not gain much information from a health history. Still. doctors will want to know if an individual has been exposed to radiation in the past. A family medical history would have no bearing on this condition, since it can’t be inherited.

During a physical exam, a doctor will ask about symptoms like fatigue, abdominal discomfort, and bone pain. The doctor will gently press on an individual’s abdomen to see if the spleen feels enlarged.

When doctors believe a patient may have chronic myeloid leukemia, they may order blood tests and a bone marrow biopsy.

• Blood tests can show whether there is a proper balance of red blood cells, white blood cells, and platelets—or whether there are too many white blood cells.
• Bone marrow biopsy, during which doctors use a needle to remove a small sample of bone and bone marrow from the hip bone. It can show whether any abnormal cells are present.
• Cytogenetic testing, which looks at the genes and chromosomes present in the blood or bone marrow, can determine whether a BCR-ABL genetic mutation is present, which indicates chronic myeloid leukemia.
• Genetic tests, such as fluorescence in situ hybridization or reverse transcription–polymerase chain reaction test, look for abnormalities or mutations within genes or chromosomes, based on blood or bone marrow samples.

Different therapies are available to treat chronic myeloid leukemia, including:

• Targeted therapy, which targets the BCR-ABL tyrosine kinase protein to flip the “on/off” switch that controls cell reproduction to “off.” Targeted therapy is the preferred treatment for this type of cancer. Several medications, known as tyrosine kinase inhibitors, are available to treat chronic myeloid leukemia.
• Interferon therapy uses interferons—substances that the immune system normally produces—to boost the action of the immune system. People with chronic myeloid leukemia are usually treated with interferon-alpha.
• Chemotherapy, which helps to kill cancer cells (although it also affects healthy cells). Different types of chemotherapy are available for people with chronic myeloid leukemia.
• Stem cell transplant, which is only offered as treatment in certain circumstances, may cure chronic myeloid leukemia. If a patient has advanced chronic myeloid leukemia and doesn’t respond to tyrosine kinase inhibitors, they may be offered a stem cell transplant if a donor (such as a sibling) is available—and if the patient doesn’t have other health complications. Doctors use high-dose chemotherapy or radiation therapy to kill leukemia cells and bone marrow cells. Afterward, new stem cells are transplanted to the bone marrow, so that it may begin to produce healthy blood cells.

About 70% of people with chronic myeloid leukemia survive 5 years or longer. Advances in treatment therapies, particularly tyrosine kinase inhibitors, have greatly improved survivorship among people with chronic myeloid leukemia. Survival rates may improve as more time passes. Some research has found that 90% of people who received the tyrosine kinase inhibitor imatinib lived for 5 years or longer.

“Yale is fortunate to have a robust network of affiliated health care centers throughout the state of Connecticut and beyond,” says Dr. Shallis. “It is through this collaborative arrangement that every patient with CML has access to a CML specialist at Yale who is an expert in the field and can help formulate an appropriate, individualized management plan.  

We make it easy for patients to have everything they need to succeed during their journey with CML, which although highly treatable, is not yet perfect and may be improved with agents and other strategies being evaluated in clinical trials, he adds.

“Furthermore, patients often require a few extra layers of support beyond that provided by a physician and/or advanced practice provider, such as nutritionists and dieticians, social workers, and other advocates,” says Dr. Shallis. “Being a Yale patient means you can get the standard of care for CML and then some, whether that means a clinical trial or having care delivered by an unparalleled team.”