Hairy Cell Leukemia

Clinic

• Hairy cell leukemia (HCL) is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes.
• It is usually classified as a subtype of chronic lymphocytic leukemia (CLL).
• Hairy cell leukemia makes up about 2% of all leukemias

Hairy cell leukemia (HCL) was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis, and its characterization was significantly advanced by Bertha Bouroncle and colleagues at the Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the malignant B cells under a microscope.

Contents

• 1Signs and symptoms
• 2Cause
• 3Pathophysiology
• 4Diagnosis
  • 4.1Classification
• 5Prevention
• 6Treatment
  • 6.1First-line therapy
  • 6.2Second-line therapy
  • 6.3Other treatments
• 7Prognosis
  • 7.1Treatment success
  • 7.2Lifespan
  • 7.3Follow-up care
• 8Epidemiology
• 9Research directions
• 10References
• 11External links

Signs / Symptoms

• In HCL, the "hairy cells" (malignant B lymphocytes) accumulate in the bone marrow, interfering with the production of normal white blood cells, red blood cells, and platelets.
• Consequently, patients may develop infections related to low white blood cell count, anemia and fatigue due to a lack of red blood cells, or easy bleeding due to a low platelet count.
• Platelet function may be somewhat impaired in HCL patients, although this does not appear to have any significant practical effect.
• Patients with a high tumor burden may also have somewhat reduced levels of cholesterol, especially in patients with an enlarged spleen.

Cause

• As with many cancers, the cause of HCL is unknown
• Human T-lymphotropic virus 2 (HTLV-2) has been isolated in a small number of patients with the variant form of HCL. In the 1980s, HTLV-2 was identified in a patient with a T-cell lymphoproliferative disease; this patient later developed HCL, but HTLV-2 was not found in the hairy cell clones. There is no evidence that HTLV-II causes any sort of hematological malignancy, including HCL.

Pathophysiology[edit]

Pancytopenia in HCL is caused primarily by marrow failure and splenomegaly. Bone-marrow failure is caused by the accumulation of hairy cells and reticulin fibrosis in the bone marrow, as well as by the detrimental effects of dysregulated cytokine production. Splenomegaly reduces blood counts through sequestration, marginalization, and destruction of healthy blood cells inside the spleen.

Hairy cells are nearly mature B cells, which are activated clonal cells with signs of VH gene differentiation. They may be related to pre-plasma marginal zone B cells or memory cells.

Cytokine production is disturbed in HCL. Hairy cells produce and thrive on TNF-alpha. This cytokine also suppresses normal production of healthy blood cells in the bone marrow.

Unlike healthy B cells, hairy cells express and secrete an immune system protein called interleukin-2 receptor (IL-2R). In HCL-V, only part of this receptor is expressed. As a result, disease status can be monitored by measuring changes in the amount of IL-2R in the blood serum.

Hairy cells respond to normal production of some cytokines by T cells with increased growth. Treatment with interferon-alpha suppresses the production of this pro-growth cytokine from T cells. A low level of T cells, which is commonly seen after treatment with cladribine or pentostatin, and the consequent reduction of these cytokines, is also associated with reduced levels of hairy cells.

In June 2011, E Tiacci et al discovered that 100% of HCL samples analysed had the oncogenic BRAF mutation V600E, and proposed that this is the disease's driver mutation. Until this point, only a few genomic imbalances had been found in the hairy cells, such as trisomy 5 had been found. The expression of genes is also dysregulated in a complex and specific pattern. The cells underexpress 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25, and 17q22-q24 and overexpress 13q31 and Xq13.3-q21. It has not yet been demonstrated that any of these changes have any practical significance to the patient.