Sandbox: patho3
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]
HCL is a slowly proliferating tumour expressing the apoptosis inhibitor BCL2
Mitogen activated protein kinases (MAPKs) have an important function in regulating HCL growth
The p38-MAPK–JNK cascade is inhibited
the MEK–ERK cascade is activated by protein kinase C (PKC) and SRC, which are constitutively active in HCL cells.
HCL cells upregulate cyclin D1 and downregulate the cyclin-dependent kinase inhibitor p27
Genetics
- The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.[3]
- 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:[3]
- 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
Associated Conditions
Gross Pathology
Microscopic Pathology
- ↑ Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.
- ↑ 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
- ↑ 3.0 3.1 3.2 Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015
- ↑ 4.0 4.1 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.