Chronic myeloid leukemia | CML || Pathology (In English )

Summary

This video delves into Chronic Myeloid Leukemia (CML), a myeloid neoplasm characterized by the excessive proliferation of myeloid lineage precursors. It covers the introduction, pathogenesis involving the Philadelphia chromosome due to a translocation between chromosomes 9 and 22, and the BCR-ABL gene fusion leading to constitutive tyrosine kinase activity. The video also discusses the morphology, including hypercellular bone marrow and leukocytosis, and clinical features like splenomegaly and fatigue. It highlights the progression from chronic phase to accelerated phase and blast crisis, resembling acute leukemia.

Takeaways

• 🌟 Chronic Myeloid Leukemia (CML) is characterized by the excessive proliferation of myeloid lineage precursors, particularly granulocytic and megakaryocytic cells.
• 🧬 The pathogenesis of CML involves a translocation between chromosomes 9 and 22, resulting in the formation of the Philadelphia chromosome, which carries the BCR-ABL fusion gene.
• 🔬 The BCR-ABL gene encodes a protein with constitutive tyrosine kinase activity, leading to the activation of growth signaling pathways and growth factor-independent proliferation.
• 📈 CML progresses slowly but can accelerate over time, leading to an accelerated phase characterized by worsening anemia and thrombocytopenia.
• 🔍 The accelerated phase may progress to blast crisis, where the blood and bone marrow resemble acute leukemia with a blast count exceeding 20%.
• 🩸 Morphologically, CML is marked by hypercellular bone marrow, the presence of sea blue histocytes, and leukocytosis with increased granulocytes.
• 📊 Patients with CML often present with massive splenomegaly due to extensive extramedullary hematopoiesis, which is a key differentiating feature from other diseases.
• 👨‍⚕️ Clinical features of CML include anemia, weakness, fatigue, and splenomegaly, with the latter presenting as a dragging sensation in the abdomen.
• 📈 The natural history of CML involves a slow progression, but if untreated, it can lead to more severe symptoms and potentially blast crisis.
• 💡 The differentiation between CML and other diseases like AML or CLL can be aided by the presence of massive splenomegaly, a characteristic finding in CML.

Q & A

What is chronic myeloid leukemia (CML)?

CML is a condition characterized by the excessive proliferation of myeloid lineage precursors over a long period of time. It is a chronic condition involving the overproduction of granulocytic and megakaryocytic precursors.

What is the Philadelphia chromosome and how is it related to CML?

The Philadelphia chromosome is a result of a translocation between chromosome 9 and chromosome 22. This translocation leads to the fusion of the ABL gene from chromosome 9 and the BCR gene from chromosome 22, creating the BCR-ABL gene. This gene encodes for a BCR-ABL protein that has constitutive tyrosine kinase activity, leading to the pathogenesis of CML.

How does the BCR-ABL protein contribute to the development of CML?

The BCR-ABL protein, resulting from the fusion of BCR and ABL genes, has a tendency to self-dimerize, which activates the ABL part's tyrosine kinase activity. This leads to the continuous phosphorylation of other proteins, activating growth signaling pathways and resulting in growth factor-independent proliferation of granulocytic and megakaryocytic precursors, characteristic of CML.

What are the clinical features observed in patients with CML?

Patients with CML typically present with symptoms such as anemia, weakness, fatigue, anorexia, and weight loss. A characteristic finding is splenomegaly, which can cause a dragging sensation in the abdomen.

What is the natural progression of CML if left untreated?

If CML is left untreated, it progresses slowly over a course of time, typically around three years, to an accelerated phase. This phase is characterized by worsening clinical features like anemia and thrombocytopenia. If the patient develops additional cytogenetic abnormalities, it can progress to a blast crisis, resembling acute leukemia.

What is the significance of the blast crisis in CML?

The blast crisis in CML signifies a phase where the disease resembles acute leukemia, with blast cells (either myeloid or lymphoid) making up more than 20% of the cells in the blood and bone marrow. This indicates a severe stage of the disease and a poorer prognosis.

What is the role of extramedullary hematopoiesis in the development of splenomegaly in CML?

In CML, the bone marrow becomes hypercellular due to excessive proliferation of myeloid precursors, leading to a displacement of normal hematopoiesis to extramedullary sites like the spleen. This extensive extramedullary hematopoiesis results in massive splenomegaly, a characteristic finding in CML.

How does the morphology of the bone marrow change in CML?

In CML, the bone marrow biopsy reveals a hypercellular condition due to the excessive proliferation of granulocytic and megakaryocytic precursors. Additionally, sea blue histocytes, which are macrophages containing wrinkled, green-blue cytoplasm, are also observed.

What is the significance of the leukocytosis seen in the blood of CML patients?

Leukocytosis, or an increased white blood cell count, is observed in CML patients due to the excessive proliferation of granulocytic precursors. This leads to an increase in neutrophils, eosinophils, basophils, myelocytes, and metamyelocytes.

What are the implications of the massive splenomegaly seen in CML patients?

Massive splenomegaly in CML patients can cause a dragging sensation in the abdomen and may lead to splenic infarction. It is a significant finding that helps differentiate CML from other hematological conditions.