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.
• As TNF α upregulates inhibitors of apoptosis such as IAP1 and IAP2, leukemic cells will demonstrate a prolonged survival due to the escape of apoptosis.
• In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes.

and up regulation of cyclin D1 ar

the is activated by protein kinase C (PKC) and SRC, which are constitutively active in HCL cells.

Malignant leukemic cells down-regulate the cyclin-dependent kinase inhibitor p27 while upregulate cyclin D1 and

Genetics

• The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.
• The BRAF V600E mutations is present among most of the patients with hairy cell leukemia (classic).
• The BRAF V600E mutations is absent among patients with hairy cell leukemia (variant).
• Molecular pathways involved in the pathogensis of hairy cell leukemia include:

• p38-MAPK-JNK molecular cascade is inhibited thus suppressing the apoptotic signaling pathways.
• MEK-ERK molecular cascade is activated thus amplifying the cytoprotective survival pathways.
• Phosphatidylinositol 3 kinase (PI3K)-AKT cascade is activated thus suppressing the apoptotic signaling pathways.