Sandbox: patho3

Pathogenesis

• Hairy cell leukemia arises from B cells, that are normally involved in the process of human immunoglobulins production.
• However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.
• Hairy cell leukemia may also infiltrate the spleen and liver.
• Extravascular hemolysis may develop due to splenic sequestration and destruction of circulating red blood cells.
• Hairy cell leukemia does not infiltrate peripheral lymph nodes.
• Bone marrow failure may develop among hairy cell leukemia patients due to:

• Malignant cells infiltrateion of the bone marrow
• Reticulin fibrosis of the bone marrow
• Dysregulated cytokine production

• The development of bone marrow failure interferes with the normal production of red blood cells and platelets among hairy cell leukemia patients.
• Production of cytokines, such as TNF α and IL-2R, provide important stimuli for malignant B cells proliferation in hairy cell leukemia.
• In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes.

Genetics

• The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.
• The BRAF V600E mutations is present in all patients with hairy cell leukemia (classic).
• The BRAF V600E mutations is not present in patients with hairy cell leukemia (variant).
• Other genes involved in the pathogenesis of hairy cell leukemia may include:

• Under expression of chromosomes 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25, and 17q22-q24.
• Over expression of chromosomes 13q31 and Xq13.3-q21