Sandbox: patho3

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Overview

Pathogenesis

  • Hairy cell leukemia arises from B cells, that are normally involved in the process of human immunoglobulins production.[1]
  • However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.[2]
  • 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:[3]
  • 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.[4]
  • In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes.[4]
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.[3]
  • 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:[4]
  • 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 suppressing the apoptotic signaling pathways.

Associated Conditions

Gross Pathology

Microscopic Pathology

  1. Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.
  2. What is Hairy Cell Leukemia? Hairy Cell Leukemia Foundation (2015) https://www.hairycellleukemia.org/about-hcl/what-is-hairy-cell-leukemia/ Accessed on October, 19 2015
  3. 3.0 3.1 Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015
  4. 4.0 4.1 4.2 Tiacci E, Liso A, Piris M, Falini B (2006). "Evolving concepts in the pathogenesis of hairy-cell leukaemia". Nat Rev Cancer. 6 (6): 437–48. doi:10.1038/nrc1888. PMID 16723990.