Chronic Myeloid Leukemia (CML) - Myeloproliferative Neoplasm (MPN) - Philadelphia Chromosome

Summary

In this video, Medicos Is Perfection (Alice) explains Chronic Myelogenous Leukemia (CML), a cancer characterized by the Philadelphia chromosome caused by a translocation between chromosomes 9 and 22. The video covers the genetic mechanisms, clinical features, stages (chronic, accelerated, blast crisis), and treatment options, particularly tyrosine kinase inhibitors. Alice emphasizes the importance of early diagnosis through blood tests, bone marrow biopsy, and cytogenetic analysis. Through a case study, the video demonstrates typical lab findings and clinical presentation of CML, offering viewers an insightful look into this chronic leukemia and its management.

Takeaways

• 😀 Chronic Myelogenous Leukemia (CML) is characterized by a translocation between chromosomes 9 and 22, resulting in the Philadelphia chromosome.
• 😀 CML is a myeloproliferative disorder that affects myeloid lineage cells (e.g., neutrophils, monocytes, basophils, eosinophils), leading to their increased proliferation.
• 😀 The BCR-ABL fusion gene created by the Philadelphia chromosome encodes a tyrosine kinase protein, which drives uncontrolled cell proliferation and prevents apoptosis.
• 😀 CML typically affects individuals aged 40-60 years and presents as a chronic leukemia with fewer blasts and more mature cells.
• 😀 The disease progresses through three phases: chronic phase (mild symptoms, responsive to treatment), accelerated phase (more immature cells, splenomegaly), and blast crisis (acute leukemia, often refractory to treatment).
• 😀 The Philadelphia chromosome is essential for diagnosing CML, and it can be detected using cytogenetic techniques like FISH or PCR.
• 😀 CML patients commonly experience symptoms like fatigue, weight loss, sweating, and splenomegaly. The spleen may be enlarged by 15 cm or more, leading to abdominal pain.
• 😀 Diagnostic tests for CML include a peripheral blood smear, complete blood count (CBC), bone marrow biopsy, and molecular analysis for the BCR-ABL fusion gene.
• 😀 The treatment for CML often involves tyrosine kinase inhibitors, which target the abnormal tyrosine kinase activity produced by the BCR-ABL fusion protein.
• 😀 CML is highly sensitive to the presence of the Philadelphia chromosome but not entirely specific, as it can also be present in some cases of acute lymphoblastic leukemia (ALL).

Q & A

What is Chronic Myelogenous Leukemia (CML)?

Chronic Myelogenous Leukemia (CML) is a type of cancer that originates from the bone marrow, specifically affecting the myeloid lineage of white blood cells, such as neutrophils, monocytes, basophils, and eosinophils. It is characterized by the presence of the Philadelphia chromosome, which results from a translocation between chromosomes 9 and 22.

What does the 9:22 translocation refer to in CML?

The 9:22 translocation in CML involves the exchange of genetic material between chromosomes 9 and 22, which fuses the ABL gene from chromosome 9 with the BCR gene on chromosome 22. This results in the BCR-ABL fusion gene, which encodes a tyrosine kinase protein that causes abnormal cell proliferation and inhibits apoptosis, leading to leukemia.

Why is CML referred to as a chronic leukemia?

CML is considered a chronic leukemia because the cancerous cells in this condition are more mature and smaller in size, unlike acute leukemias, which have immature and larger blasts. In CML, the disease progresses slowly, and patients are usually older, with a relatively mild onset of symptoms.

What are the common clinical features of CML?

Common clinical features of CML include fatigue, weight loss, sweating, painless lymphadenopathy, hepatomegaly, and splenomegaly. In fact, 90% of CML patients have splenomegaly, often resulting in abdominal pain and an increased risk of spleen infarction due to compromised blood supply.

How is the Philadelphia chromosome relevant in CML diagnosis?

The Philadelphia chromosome is a key diagnostic feature of CML, formed by the 9:22 translocation. It is highly sensitive in detecting CML, meaning its presence almost certainly indicates the disease. However, it is not specific because other conditions, such as acute lymphoblastic leukemia (ALL), can also involve the Philadelphia chromosome.

What are the phases of CML and how do they progress?

CML progresses through three phases: the chronic phase, the accelerated phase, and the blast crisis. In the chronic phase, patients are often asymptomatic or have mild symptoms. The accelerated phase is marked by splenomegaly and basophilia, while the blast crisis resembles acute leukemia, either AML or ALL, and is typically refractory to treatment and associated with a poor prognosis.

What role does the BCR-ABL fusion protein play in CML?

The BCR-ABL fusion protein is a tyrosine kinase that disrupts normal cell functions, leading to uncontrolled proliferation of leukemic cells and inhibiting normal cell death (apoptosis). This contributes to the rapid expansion of cancerous white blood cells in CML.

What laboratory findings are typically seen in CML?

In CML, laboratory findings often include normocytic anemia, thrombocytosis, and an elevated white blood cell count, sometimes reaching up to 600,000 cells/μL. The peripheral blood smear may show neutrophilia with few or no blasts, and basophilia may be present as the disease progresses.

What is the significance of the leukocyte alkaline phosphatase (LAP) score in CML?

The LAP score helps distinguish between leukemia and a leukemoid reaction. In CML, the LAP score is low because the leukemic cells are abundant but not functional. In contrast, a high LAP score indicates a normal or reactive increase in white blood cells.

How do tyrosine kinase inhibitors (TKIs) help in the treatment of CML?

Tyrosine kinase inhibitors (TKIs) target the BCR-ABL fusion protein, inhibiting its abnormal activity and thereby reducing the uncontrolled proliferation of leukemic cells. TKIs are effective in treating CML, particularly during the chronic phase, by helping to manage the disease and prevent progression to the accelerated or blast crisis phases.