Chronic granulocytic leukemia

Chronic Granulocytic Leukemia

Chronic Granulocytic Leukemia (CGL), also known as Chronic Myeloid Leukemia (CML), is a type of cancer that affects the blood and bone marrow. It is characterized by the overproduction of myeloid cells, which are a type of white blood cell. CGL is a clonal bone marrow stem cell disorder in which a proliferation of mature granulocytes (neutrophils, eosinophils, and basophils) and their precursors is found.

Pathophysiology

CGL is primarily associated with a genetic abnormality known as the Philadelphia chromosome, which results from a translocation between chromosomes 9 and 22. This translocation creates a fusion gene called BCR-ABL1, which encodes a tyrosine kinase protein that is constitutively active. The BCR-ABL1 protein leads to increased cell division and reduced apoptosis, contributing to the accumulation of myeloid cells in the bone marrow and peripheral blood.

Clinical Presentation

Patients with CGL often present with symptoms such as fatigue, weight loss, night sweats, and splenomegaly. Some patients may be asymptomatic and are diagnosed incidentally through routine blood tests showing elevated white blood cell counts.

Diagnosis

The diagnosis of CGL is typically confirmed through:

• Complete blood count (CBC) showing leukocytosis with a left shift.
• Bone marrow biopsy revealing hypercellularity with increased myeloid cells.
• Cytogenetic analysis or fluorescence in situ hybridization (FISH) to detect the Philadelphia chromosome.
• Polymerase chain reaction (PCR) to identify the BCR-ABL1 fusion gene.

Treatment

The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of CGL. Imatinib was the first TKI approved for CGL and remains a standard first-line treatment. Other TKIs, such as dasatinib and nilotinib, are also used, especially in cases of resistance or intolerance to imatinib.

Prognosis

The prognosis for patients with CGL has improved significantly with the use of TKIs. Many patients achieve long-term remission and have a near-normal life expectancy. However, some patients may progress to the accelerated phase or blast crisis, which are more challenging to treat and have a poorer prognosis.

Also see

• Leukemia
• Philadelphia chromosome
• Tyrosine kinase inhibitors
• Bone marrow biopsy