Researchers from the University of Toronto had found in earlier studies that low-density lipoprotein (LDL) levels are elevated in up to 75% of patients with chronic lymphocytic leukemia (CLL). They also found that statins delayed the need for chemotherapy in those patients by nearly 3 years. They furthered their research using data on 2,124 patients with CLL and 7,935 controls in a population-based, case-control study. The researchers found a significantly higher incidence of hypercholesterolemia before CLL was diagnosed and a survival benefit of 3.7 years for patients taking statins.
In a new study to understand why hypercholesterolemia is apparently a tumor promoter for CLL, researchers first used an in vitro model of the “microenvironments” called pseudofollicles, where CLL cells proliferate. The researchers purified CLL cells from patients and activated them in lipid-poor conditions with interleukin-2 and resiquimod to represent stimulatory signals in pseudofollicles.
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Adding LDLs increased viable cell numbers and signal transduction in molecules that mediate growth and proliferation of CLL cells.
To determine whether the effects were unique to CLL, the researchers conducted a similar experiment using peripheral blood mononuclear cells from donors without CLL. Their results suggested that normal blood cells handled cholesterol from LDLs in a different way than did CLL cells.
In another experiment, the researchers used circulating CLL cells from an additional cohort of 30 patients, including 11 who had been taking statins for at least 6 months. Cholesterol content of circulating CLL cells correlated directly with blood LDL levels, suggesting that LDLs may enhance proliferative responses of CLL cells to inflammatory signals. Statin use was associated with lower cholesterol in CLL cells, fewer circulating leukemia cells, and longer doubling times in vivo.