[Apoptosis in pathogenesis of B-cell chronic lymphocytic leukemia].
B-cell chronic lymphocytic leukemia (B-CLL), a clonal expansion of B CD5+ cells, is the most frequent type of adult leukemia in western countries. Accumulation of neoplastic B-cells is caused not by their higher proliferation rate, but by their prolonged life-span due to dysregulation of apoptosis. Many proteins act as inducers or inhibitors in controlling apoptosis. A high level of antiapoptotic BCL-2 protein is detected in B cells of B-CLL. Other factors, such as NF-kappaB, PI-3K and PKC, are also involved in the inhibition of malignant cell apoptosis. A high level of p27kip1, an inhibitor of cyclin-dependent kinase that correlates with the degree of in vitro apoptosis, is found in B-CLL cells. The autologous interaction between BAFF, APRIL, and their ligands may also be involved in apoptosis inhibition in B-CLL. Some external factors e.g. cytokines, may suppress apoptosis of malignant cells. IL-4, IL-2, IFN-gamma, and TNF are proven inhibitors, while IL-5 and IL-10 are inducers of apoptosis of these cells. Even though there are reports characterizing some mechanisms of B-CLL cell apoptosis, relatively less is still known about the complex regulation of this process. This requires more precise research, as new anti-leukemic drugs influence the regulation of apoptosis of neoplastic B lymphocytes.
Podhorecka
Monika
M
Klinika Hematoonkologii i Transplantacji Szpiku Akademii Medycznej w Lublinie.
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007376:Interleukin-2; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma