What is the pathophysiology of hairy cell leukemia (HCL)?

Updated: Sep 16, 2018
  • Author: Emmanuel C Besa, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP  more...
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The abnormal cell in hairy cell leukemia (HCL) is a clonal B-cell lymphocyte (see image below). This cell infiltrates the reticuloendothelial system and interferes with bone marrow function, resulting in bone marrow failure or pancytopenia. [3, 4] The hairy cell also infiltrates the liver and spleen, resulting in organomegaly.

Blood film at × 400 magnification. This image demo Blood film at × 400 magnification. This image demonstrates a lymphocytosis and an absence of any other type of blood cell (pancytopenia). The characteristic cytoplasmic projections are already visible. Photographed by U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.

The pathogenesis of HCL was clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. [5] By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior. Accompanying mutations of the KLF2 transcription factor or the CDKN1B/p27 cell cycle inhibitor are recurrent in 16% of patients with HCL and likely cooperate with BRAF-V600E in HCL pathogenesis. [6]  

The etiology of HCL has not been determined, although some investigators suggest that exposures to benzene, organophosphorus insecticides, or other solvents may be related to disease development. This hypothesis has not been confirmed by other reports, although a French study that evaluated occupational exposure to pesticides and lymphoid neoplasms in men appears to support the hypothesis that occupational pesticide exposures may not only be involved in HCL, Hodgkin lymphoma, and multiple myeloma, but also may play a role in non-Hodgkin lymphoma. [7] Further research is needed.

Other suggested etiologic associations include exposure to radiation, agricultural chemicals, and wood dust, and a previous history of infectious mononucleosis.

Overexpression of cyclin D1 protein, an important cell-cycle regulator, has been observed in HCL and may play a role in the molecular pathogenesis of the disease.

Accumulation of hairy cells in the bone marrow, liver, and spleen, with very little lymph node involvement, is characteristic of HCL. This pattern probably results from the expression of the integrin receptor alpha4-beta1 by the hairy cells and the interaction of the receptor with the vascular adhesion molecule-1 (VCAM-1) found in splenic and hepatic endothelia, bone marrow, and splenic stroma.

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