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B cells and B cell cancer research

Terms in this set (19)

B-CLL is characterized by proliferation and accumulation of small, mature, long-lived lymphocytes in blood, marrow and lymph nodes and spleen. So the difference compaired to acute myeloid leukemia is that the disease is mediated by differentiated B cells.
Key elements of its pathogenesis are inhibition of apoptosis (increase in anti-apoptotic protein bcl-2), degeneration of proliferation and interactions with the microenvironment (in vitro CLL cells die).

Basic facts:
- most common leukemia in western world
- males are more often affected than females with a ratio of 2:1
- disease of older people (60-80 yrs)
- CLL cells can carry mutated or unmutated IGHV genes
- patients with mutated IGHV genes: significantly longer survival
- death from infections, BM failure, high-grade
- transformation (richter´s syndrome/transformation)
- CLL is a clonal expansion of CD5+ cells in blood an lymphoid compartments
- 6% of normal, elderly people develop CD5+ monoclonal B cell lymphocytosis (MBL)
-> It is considered that B1 cells are the origin of CLL
- genetic factors play a role (mutations in SF3B1, NOTCH1, TP53, ...)
Immunophenotype:
- 90% of patients have a weak expression of surface Ig (kappa or lambda light chain, IgM, IgD)

Clinical symptoms
- often asymptomatic (40%) and diagnosed by chance with blood lymphocytosis and no specific symptoms of physical signs
- unspecific symptoms: swollen lymph nodes, night sweat, fever, extreme fatigue, reduced exercises tolerance, weight loss, recurrent infections (most common cause of death)
- specific symptoms: splenomegaly, lymphadenopathy, hepatomegaly

diagnosis:
- first suspected by a diagnosis of lymphocytosis (increase of white blood cells), frequently an incidental finding on a routine physician visit
Confirmatory test:
- flow cytometry (immunophenotype), light chain restriction, co-expression of CD5
- peripheral blood smear: smudged cells = small, broken cells (lack cytoskeletal protein) these cells are fragile when smeared onto glass slides
- clonal accumulation
- genetics