Chronic Myeloid Leukemia (CML), also known as chronic myelogenous leukemia, is a type of cancer originating in the blood-forming cells of the bone marrow.
A genetic change occurs in an early (immature) myeloid cell (cells that produce red blood cells, platelets, and most white blood cells except lymphocytes).
This change results in an abnormal gene called BCR-ABL, transforming the cell into a CML cell.
The leukemia cells proliferate, accumulating in the bone marrow and spilling into the blood; they can also settle in other areas of the body, such as the spleen.
CML is typically slow-growing but can evolve into a fast-growing acute leukemia that is difficult to treat.
American Cancer Society's 2023 estimates for CML in the United States:
Approximately 8,930 new cases will be diagnosed (5,190 in men, 3,740 in women).
About 1,310 deaths are expected (780 men, 530 women).
CML accounts for about 15% of all new leukemia cases.
Approximately 1 in 526 people in the United States will develop CML during their lifetime.
The average age at CML diagnosis is approximately 64 years.
Almost half of CML cases are diagnosed in individuals aged 65 and older.
CML primarily affects adults and is rare in children.
While exposure of skin to strong sunlight is a risk factor for skin cancer and smoking is a risk factor for several cancers, having risk factors doesn't guarantee the disease, and many affected individuals may have no known risk factors.
Established risk factors for CML:
Radiation exposure: High-dose radiation exposure (e.g., atomic bomb survivors or nuclear reactor accident victims) increases CML risk.
Age: CML risk increases with age.
Sex: CML is slightly more prevalent in males, though the underlying cause is unknown.
Other factors like smoking, diet, chemical exposure, or infections do not appear to affect CML risk.
CML does not typically run in families.
Normal cell growth and function depend on the information within the cell's chromosomes.
Chromosomes consist of long DNA molecules containing our genes.
Genes dictate how our cells function, and we inherit our DNA from our parents.
Gene mutations affect more than appearances.
During cell division, when cells copy DNA, errors can occur, leading to mutations that affect genes.
Certain genes, called oncogenes, promote cell growth and division.
Tumor suppressor genes slow down cell division or cause cells to die at the correct time.
Cancers may result from DNA changes (mutations) that activate oncogenes or deactivate tumor suppressor genes.
Scientists have made significant progress, in recent years, in elucidating how specific DNA changes can cause normal bone marrow cells to transform into leukemia cells; this is more understood in CML than any other cancer.
Human cells contain 23 pairs of chromosomes.
Most CML cases initiate during cell division when DNA is exchanged between chromosomes 9 and 22.
A translocation occurs where part of chromosome 9 moves to 22, and vice versa, resulting in a shorter chromosome 22 called the Philadelphia chromosome.
The Philadelphia chromosome is present in the leukemia cells of almost all CML patients.
The DNA swapping leads to the creation of a new gene (oncogene) called BCR-ABL, which produces the BCR-ABL protein (a tyrosine kinase).
The BCR-ABL protein causes CML cells to proliferate uncontrollably.
Rarely, CML patients may have the BCR-ABL oncogene without the Philadelphia chromosome, suggesting the BCR-ABL gene formed differently.
Very rarely, individuals who appear to have CML lack both the Philadelphia chromosome and the BCR-ABL oncogene; these individuals may have other unknown oncogenes responsible for their disease and may not truly have CML.
Inherited DNA mutations do not cause CML; CML-related DNA changes arise during a person's lifetime rather than being inherited.
The American Cancer Society advises screening tests for certain cancers in asymptomatic individuals, as early detection improves treatment outcomes.
Currently, no routine screening tests are recommended for the early detection of CML.
CML may be incidentally discovered during routine blood tests performed for other purposes, such as a routine physical examination, when a high white blood cell count is observed in the absence of symptoms.
Reporting potential CML symptoms is crucial.
CML symptoms are often vague and commonly caused by other conditions.
Symptoms may include:
Weakness
Fatigue
Night sweats
Weight loss
Fever
Bone pain (due to leukemia cells spreading from the marrow cavity to the surface or into the joint)
Enlarged spleen (palpable as a mass under the left ribcage)
Pain or fullness in the abdomen
Feeling full after consuming a small amount of food
These symptoms are not exclusive to CML and can occur in other cancers and non-cancerous conditions.
Anemia (shortage of red blood cells) leads to weakness, fatigue, and shortness of breath.
Leukopenia increases the risk of infections; leukemia cells do not protect against infection like normal white blood cells, despite high white blood cell counts.
Neutropenia increases the risk of severe bacterial infections.
Thrombocytopenia can cause easy bruising or bleeding, including frequent or severe nosebleeds and bleeding gums.
Conversely, some CML patients have thrombocytosis (too many platelets); however, dysfunctional platelets can still result in bleeding and bruising.
The most common sign of CML is an abnormal white blood cell count.
WB cell counts
Most CML patients have elevated white blood cell counts with a high proportion of early (immature) cells called myeloblasts or blasts.
Doctors assess the size and shape of cells and check for the presence of granules (small spots in some white blood cells).
An important diagnostic factor is whether the cells appear mature (like normal circulating cells) or immature (lacking features of normal cells).
CML patients may exhibit low levels of red blood cells or blood platelets.
These findings can suggest leukemia, but confirmation requires additional blood or bone marrow tests.
Bone marrow biopsy
Chemistry tests
Genetic tests
Imaging tests
Most cancers are staged based on tumor size and the extent of cancer spread; however, CML, being a bone marrow disease, is not staged like most cancers.
The prognosis for CML depends on disease phase, blast count in the bone marrow, patient age, blood counts, and spleen size.
CML is classified into three phases that help predict prognosis, primarily based on the percentage of immature white blood cells (blasts) in the blood or bone marrow.
Patients in the chronic phase typically have less than 10% blasts in their blood or bone marrow samples.
These patients usually have mild or no symptoms.
Most patients are diagnosed in the chronic phase.
Patients are considered to be in the accelerated phase if any of the following criteria are met:
Blood samples contain 15% or more, but fewer than 30% blasts.
Basophils account for 20% or more of the blood.
Combined blasts and promyelocytes constitute 30% or more of the blood.
Very low platelet counts (100 \times 1,000/mm^3 or less) not caused by treatment.
New chromosome changes are present in leukemia cells with the Philadelphia chromosome.
Accelerated phase CML may present with symptoms such as fever, poor appetite, and weight loss.
Accelerated phase CML does not respond as favorably to treatment as chronic phase CML.
In this phase, bone marrow and/or blood samples contain 20% or more blasts.
Large clusters of blasts are observed in the bone marrow.
Blast cells have spread to tissues and organs beyond the bone marrow.
These patients often have fever, poor appetite, and weight loss.
In the blast phase, CML behaves similarly to acute leukemia.
Besides the CML phase, other factors can help predict survival outcomes and inform treatment decisions.
Factors associated with shorter survival times are considered adverse prognostic factors.
Accelerated or blast phase
Enlarged spleen
Areas of bone damage due to leukemia growth
Increased basophil and eosinophil counts in blood samples
Very high or very low platelet counts=
Age 60 years or older
Multiple chromosome changes in CML cells
Highly effective CML treatments became available in 2001.
Long-term survival data for patients treated with these drugs is still being collected.
Most patients treated with these drugs since 2001 are still alive.
One study of CML patients treated with imatinib (Gleevec®) showed approximately 90% survival at 5 years after starting treatment.
Most of these patients had normal white blood cell counts and chromosome studies after 5 years on the drug.