Chronic Myeloid Leukemia (CML) is a cancer that begins in the bone marrow, the soft, spongy tissue inside bones where blood cells are produced. It specifically affects blood-forming stem cells, leading to an uncontrolled growth of certain white blood cells. CML is considered a blood cancer because it originates in these blood-producing tissues and impacts cells circulating throughout the bloodstream.
What is Chronic Myeloid Leukemia (CML)?
Chronic Myeloid Leukemia develops when an abnormal change occurs in a hematopoietic stem cell within the bone marrow. This leads to the overproduction of myeloid cells, a type of white blood cell. The defining characteristic of CML is the presence of the Philadelphia chromosome (Ph chromosome), which is acquired during a person’s lifetime. This abnormal chromosome results from a genetic rearrangement where a piece of chromosome 9 attaches to chromosome 22.
This rearrangement creates the BCR-ABL1 gene. The BCR-ABL1 gene produces a tyrosine kinase protein that is constantly active, signaling blood cells to grow and divide without proper control. This uncontrolled proliferation of abnormal white blood cells fills the bone marrow, crowding out healthy blood-forming cells. These abnormal cells then enter the bloodstream, circulating throughout the body.
How CML Affects the Body’s Organs
Chronic Myeloid Leukemia does not spread or “metastasize” like solid tumors by forming new growths in distant organs. Instead, abnormal white blood cells from the bone marrow travel through the bloodstream and accumulate in various organs and tissues. This accumulation leads to organ enlargement and potential dysfunction, due to the sheer volume of abnormal cells infiltrating existing tissues.
The spleen is commonly affected, often becoming significantly enlarged (splenomegaly). This enlargement can cause discomfort, pain in the upper left abdomen, or a feeling of fullness. The liver can also enlarge (hepatomegaly) due to cell accumulation. Lymph nodes may swell as they become infiltrated with leukemic cells.
Less commonly, CML cells can form masses outside the bone marrow and blood, known as extramedullary disease or myeloid sarcoma. This occurs when abnormal cells proliferate in tissues like the skin, kidneys, or gastrointestinal tract. Extramedullary involvement is infrequent, especially in early stages, and more often associated with advanced CML.
Phases of CML Progression
CML typically progresses through distinct phases: chronic, accelerated, and blast crisis.
Most individuals are diagnosed during the chronic phase, characterized by relatively slow disease progression. In this phase, abnormal cells make up less than 10% of cells in the blood and bone marrow, and many people experience mild or no symptoms.
As the disease advances, it may enter the accelerated phase, where abnormal cells increase, typically reaching 10% to 19% of cells in the blood or bone marrow. Symptoms often become more pronounced, including increased fatigue, weight loss, and more significant organ enlargement. This phase indicates a greater burden of abnormal cells and a reduced response to treatment.
The most advanced and aggressive phase is blast crisis, which behaves similarly to acute leukemia. In blast crisis, immature blast cells constitute 20% or more of cells in the blood or bone marrow, or may have spread extensively to other organs and tissues. Symptoms are severe, including high fever, bone pain, and significant organ enlargement, reflecting rapid proliferation and widespread accumulation of leukemic cells.
Detecting and Managing Organ Involvement in CML
Detecting organ involvement in CML relies on diagnostic methods. A physical examination can identify an enlarged spleen or liver. Blood tests, such as a complete blood count (CBC), often show an increased white blood cell count and other abnormalities indicative of CML’s impact on blood cell production.
Specialized genetic tests, including cytogenetics or molecular tests like PCR, confirm the Philadelphia chromosome or the BCR-ABL1 gene in blood or bone marrow samples. Imaging tests, such as ultrasound, CT scans, or MRI, assess the size of organs like the spleen and liver, helping identify the extent of organ infiltration. These tests help monitor the disease’s progression and its effects.
Treatment strategies for CML aim to control abnormal cell proliferation, preventing or reversing organ-related complications. Tyrosine kinase inhibitors (TKIs) are a common first-line treatment that specifically target the BCR-ABL1 protein, effectively reducing abnormal cells and often shrinking enlarged organs. Regular monitoring through blood tests and physical exams tracks the disease’s response to treatment and manages ongoing organ involvement, improving outcomes for many individuals with CML.