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Human natural killer cells are a population of large
granular lymphocytes which can lyses tumor target cells in vitro without
prior sensitization and with no major histocompatibility complex restriction.
Lymph proliferative diseases of large granular lymphocytes can arise from T
lymphocytes or natural killer cells. Large granular lymphocyte leukemia’s
derived from T lymphocytes generally follow an indolent course with a median
survival time exceeding many years. However, large granular leukemia’s
involving natural killer cells are typically very aggressive and patients have
a median survival time of two months due to being refractory to multi-agent
chemotherapy. The World Health Organization classifies natural killer cell
malignancies into three categories, including aggressive natural killer cell
leukemia, extra nodal natural killer lymphoma and blastic natural killer cell
lymphoma.
Though studies are sparse, natural killer cell
malignancies seem to be relatively rare in Caucasians, but the incidence rises
significantly in Asian and South American populations. One potentially
promising approach is through the use of statins drugs. Statins have been used
to lower LDL cholesterol levels in those with hypercholesterolemia and have
been shown to have a limited number of side effects. Commonly prescribed
statins include lovastatin, simvastatin, atorvastatin; fluvastatin,
pravastatin, and rosuvastatin calcium. It shown that statins can have
anti-inflammatory and immune modulator effects. In addition, statins may have
potent anti-tumor properties.
In terms of the effect of statins on natural killer cell
leukemias, a clinical case report noted that treatment with a farnesyl transferase
inhibitor, which interrupts the mevalonate pathway farther downstream than the
statins, resulted in clinical improvement and, importantly, a reduction of
pulmonary artery hypertension. The pulmonary hypertension has been connected to
damage to the pulmonary endothelial cells as a result of leukemic natural
killer cell cytotoxicity. The novel effect of statins on leukemia cells is a
new and potentially exciting field of research.
In the current research utilized the cell line YT-INDY to investigate the effect of
statins on natural killer leukemic cells. The parental YT cell line is an
interleukin-2-independent human leukemia natural killer cell line that has been
used in numerous studies to investigate normal natural killer cell function. YT
cells were isolated originally from a boy with
acute lymphoblastic lymphoma. Investigations were performed because aggressive
natural killer cell leukemias are devastating diseases which are nearly always
fatal within weeks or, at best, a few months of diagnosis. Multi-agent
chemotherapy has failed in the majority of patients with this disease.
Therefore, new approaches to treatment must be developed that can provide a
cure or significant life extension.
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