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Background: B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease at the clinical, molecular and cellular level. B-CLL is characterized by the accumulation of mature B lymphocytes in blood, secondary lymphoid tissues, and bone marrow, where the balance between proliferation and apoptosis is disrupted. Stimulatory and growth signals from the environment of B-CLL cells have been implicated in this disease allowing the B-cells to avoid apoptosis and proliferate; however, the specific array of microenvironment signals is unknown. Apolipoproteins A-1 and CIII, play an important role in cholesterol and triglyceride metabolism, respectively. Apolipoprotein H has been implicated in a variety of physiologic pathways including lipoprotein metabolism, coagulation, and the production of antiphospholipid autoantibodies.

Purpose: To determine whether plasma concentration of selected apolipoproteins in patients with B-CLL deviates from values of normal controls.

Methods: We collected a detailed clinical history and evaluated the plasma of 45 patients with B-CLL (21, stage 0 and 24, stages 1-4) and 20 sex-matched, disease- and aged-adjusted control subjects for apolipoproteins A-1, CIII, and H. Measurements were performed using a multiplex assay based on Luminex technology. The performance characteristics of these tests were validated by Rules-Based Medicine, Inc. Essentially, this multiple assay measures proteins in a manner similar to standard sandwich ELISA.

Results: Plasma levels of apolipoprotein A-1 (.37 ± .1 mg/mL versus .3 ± .09 mg/mL; p= .021), apolipoprotein CIII (75.86 ± 36.07 ug/mL versus 57.95 ± 27.24 ug/mL; p= .009), and apolipoprotein H (326.24 ± 71.36 ug/mL versus 223.67 ± 54.39 ug/mL; p= <.0001) were increased significantly in B-CLL patients when compared to the control group. In addition, only apolipoprotein H was found to be increased significantly in B-CLL patients stage 0 when compared to stages 1-4 (358.95 ± 66.2 ug/mL versus 297.63 ± 64.02 ug/mL; p= <.0026). There was no correlation between plasma levels of the selected apolipoproteins and weight, body mass index, LDH, and cholesterol among the B-CLL patients.

Conclusions: The results showed that patients with B-CLL have significantly higher circulating levels of apolipoproteins A-1, CIII, and H. Further studies are necessary to determine the correlation between the plasma levels of these molecules and B-CLL progression and prognosis.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA