Chronic Myeloid Leukemia

What is chronic myeloid leukemia (CML)?

A chronic myeloproliferative neoplasm characterized by overproduction of mature myeloid cells, especially neutrophils.

Which cell lineage predominates in CML?

Myelocytic lineage including neutrophils, basophils, and eosinophils.

What is the hallmark genetic abnormality in CML?

t(9;22) translocation forming the Philadelphia chromosome.

What fusion gene is created in CML?

BCR-ABL fusion gene.

What is the function of BCR-ABL?

Constitutively active tyrosine kinase causing uncontrolled proliferation.

What is the key pathophysiology of CML?

Unregulated tyrosine kinase signaling leading to increased cell growth and defective DNA repair.

What is the only known risk factor for CML?

Ionizing radiation.

What age group is most affected by CML?

Adults aged 50–60 years.

What are the two main phases of CML?

Chronic phase and blast crisis.

What characterizes the chronic phase of CML?

Slow progression with low blast count and often minimal symptoms.

What percentage of patients present in chronic phase?

Approximately 85–90%.

How long does untreated chronic phase typically last?

About 3–4 years.

What are common symptoms in chronic phase CML?

Fatigue and splenomegaly-related fullness.

What causes splenomegaly in CML?

Extramedullary hematopoiesis.

What is blast crisis in CML?

Transformation into an acute leukemia with >20% blasts.

What symptoms occur in blast crisis?

Fever, weight loss, night sweats, bone pain, and severe fatigue.

What is the prognosis of blast crisis?

Poor, with survival of weeks to months.

What is seen on CBC in CML?

Marked leukocytosis with increased neutrophils, basophils, and eosinophils.

What is the typical WBC count in CML?

Often around 100,000/mm³ but can reach up to 1,000,000/mm³.

What is a left shift in CML?

Presence of immature neutrophil precursors in peripheral blood.

What is the blast percentage in chronic phase CML?

Usually <10%.

What distinguishes CML from acute leukemia in blast count?

CML has low blasts initially, while acute leukemia has high blasts.

What is a key peripheral smear finding in CML?

Neutrophilic leukocytosis with left shift and basophilia.

What is basophilia and why is it important in CML?

Increased basophils, a key diagnostic clue since they are normally rare.

What enzyme is decreased in CML neutrophils?

Leukocyte alkaline phosphatase (LAP).

What is the significance of low LAP in CML?

Helps distinguish CML from reactive leukocytosis.

What is seen in bone marrow in CML?

Hypercellular marrow with predominance of neutrophils and precursors.

What happens to normal hematopoietic cells in CML?

They are crowded out by neoplastic cells.

What happens to RBCs and platelets over time in CML?

They may decrease as disease progresses, leading to anemia and thrombocytopenia.

What complication can arise from high WBC turnover?

Gout due to increased uric acid.

What causes bone pain in CML?

Bone marrow expansion.

What diagnostic tests are used for CML?

CBC, peripheral smear, bone marrow biopsy, and genetic testing.

What confirms the diagnosis of CML?

Detection of the Philadelphia chromosome or BCR-ABL gene.

What genetic tests are used for CML diagnosis?

Cytogenetics, FISH, and RT-PCR.

What is the first-line treatment for CML?

Tyrosine kinase inhibitors (TKIs).

What is the mechanism of TKIs?

Block BCR-ABL tyrosine kinase activity.

What is the first-line TKI used in CML?

Imatinib.

What are alternative TKIs for CML?

Nilotinib, dasatinib, bosutinib, and ponatinib.

How have TKIs changed CML prognosis?

Transformed it into a chronic manageable condition.

When is chemotherapy used in CML?

In advanced or TKI-resistant disease.

When is bone marrow transplant considered in CML?

In younger patients or advanced disease.

What indicates progression to blast crisis?

Increased blast cells in blood or marrow >20%.

What type of leukemia can blast crisis resemble?

Usually AML, but can be ALL in some cases.

Why can blast crisis be lymphoid in origin?

Mutation may arise in an early stem cell capable of lymphoid differentiation.

What is the hallmark clinical takeaway of CML?

A chronic myeloproliferative disorder driven by BCR-ABL tyrosine kinase with progression to blast crisis if untreated.