CML | Unified In A Fight

Chronic Myeloid Leukemia

Introduction

Chronic Myeloid Leukemia (CML), also known as chronic myelogenous leukemia, is a type of cancer that develops in the blood-forming cells of the bone marrow. It is caused by a genetic mutation that affects early myeloid cells, which are responsible for producing red blood cells, platelets, and most white blood cells (excluding lymphocytes). This mutation results in the formation of the BCR-ABL gene, which converts these cells into leukemia cells. These abnormal cells multiply uncontrollably, accumulating in the bone marrow and eventually spreading into the bloodstream. Over time, CML can also affect other organs, such as the spleen. Although CML usually progresses slowly, it can transform into an aggressive acute leukemia, making it more difficult to treat. CML primarily occurs in adults, but in rare cases, it can also affect children, who typically receive similar treatment to adults.

Symptoms of CML

CML often progresses without noticeable symptoms in its early stages and is frequently discovered during routine blood tests. As the disease advances, symptoms may develop as the number of blast cells (immature white blood cells) increases, crowding out healthy cells and impairing normal blood cell function. These symptoms can include:

Bone pain
Easy bruising or bleeding
Fatigue
Fever
Feeling full after eating small amounts of food
Loss of appetite
Weight loss without trying
Pain or fullness below the ribs on the left side (due to an enlarged spleen)
Excessive sweating, particularly at night
Blurry vision (caused by bleeding in the back of the eye)

Phases of CML

CML progresses through three phases, based on the percentage of blast cells in the blood and bone marrow:

Chronic Phase: Less than 10% of cells in the blood and bone marrow are blast cells. This phase is typically more manageable and responds well to treatment.

Accelerated Phase: 10% to 19% of cells are blast cells. Symptoms begin to worsen as the disease becomes more resistant to treatment.

Blastic Phase (Blast Crisis): 20% or more of the cells in the blood or bone marrow are blast cells. This phase behaves similarly to acute leukemia, causing severe symptoms like fatigue, fever, and an enlarged spleen. It is much harder to treat effectively.

CML can relapse after treatment, leading to a recurrence of the disease with increasing numbers of blast cells.

Genetic Basis: The Philadelphia Chromosome

Human cells contain 23 pairs of chromosomes, which carry genetic information. In CML, a genetic abnormality occurs in which part of chromosome 9 swaps places with a segment of chromosome 22, creating a shorter chromosome 22, known as the Philadelphia chromosome. This chromosomal abnormality is present in 90% of individuals with CML and plays a central role in the development of the disease by producing the BCR-ABL fusion gene that drives leukemia cell growth.

Diagnosis Tests for CML

A variety of tests are used to diagnose CML and monitor its progression, including:

Physical Exam and Medical History: A detailed physical examination is performed to check for signs of disease, such as an enlarged spleen, and to review the patient's medical history.

Complete Blood Count (CBC) with Differential: This test measures the number and types of red blood cells, white blood cells, and platelets, along with hemoglobin levels (which carry oxygen). The proportions of different types of cells can help identify abnormalities.

Blood Chemistry Studies: These tests measure the levels of substances released by organs and tissues, which may indicate disease if they are too high or too low.

Bone Marrow Aspiration and Biopsy: A sample of bone marrow, blood, and bone is extracted and examined under a microscope for abnormal cells.

Cytogenetic Analysis: This test examines the chromosomes in a sample of blood or bone marrow to detect abnormalities like the Philadelphia chromosome.

FISH (Fluorescence in situ Hybridization): This test uses fluorescent dyes to detect specific genes or chromosome regions in cells. It helps diagnose cancer and guide treatment plans by highlighting genetic abnormalities.

Reverse Transcription–Polymerase Chain Reaction (RT-PCR): This highly sensitive test measures the activity of specific genes and detects minute amounts of leukemia cells by identifying the genetic changes that cause CML.

Treatment

Treatment for CML varies based on the phase of the disease, the patient's age, and overall health. Some key treatments include:

Targeted Therapy: This treatment uses drugs to specifically target the abnormal BCR-ABL protein produced by leukemia cells. Drugs such as imatinib, dasatinib, nilotinib, ponatinib, bosutinib, and asciminib are commonly used. These drugs inhibit the tyrosine kinase enzyme, which helps leukemia cells grow, thereby controlling the disease.

Chemotherapy: Chemotherapy kills cancer cells or stops them from dividing. It can be administered orally or via injection and is used in cases where the disease progresses despite targeted therapy.

Immunotherapy: This treatment strengthens the body’s immune response to cancer, using substances either naturally produced by the body or created in a laboratory to boost the immune system's ability to destroy cancer cells.

Interferon: This drug slows the growth of cancer cells and can help control the disease, particularly in cases where tyrosine kinase inhibitors are ineffective.

High-Dose Chemotherapy with Stem Cell Transplant: High doses of chemotherapy are used to kill cancer cells, but this also destroys healthy blood-forming cells. After chemotherapy, a stem cell transplant is performed to replace the destroyed cells with healthy ones from a donor or from the patient’s own previously stored stem cells.

Donor Lymphocyte Infusion (DLI): Following a stem cell transplant, donor lymphocytes (a type of white blood cell) may be infused into the patient to help attack any remaining leukemia cells.

Splenectomy (Surgery): In some cases, surgery may be performed to remove the spleen if it becomes enlarged and causes discomfort or complications.

Conclusion

Ultimately, Chronic Myeloid Leukemia is a form of blood cancer, primarily caused by a genetic mutation resulting in the Philadelphia chromosome and the BCR-ABL fusion gene. Targeted therapies are used to treat CML, and understanding the symptoms, diagnostic tools, genetic basis, and treatment options is essential for managing the disease effectively.

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