Cholesterol Homeostasis in Isolated Lymphocytes: a Differential Correlation Between Male Control and Chronic Lymphocytic Leukemia Subjects

Document Type: Research Articles

Authors

1 KLE University, J N Medical College, Belagavi, Karnataka, India

2 Government Medical College, Haldwani Distt- Nainital, Uttarakhand. India

3 Department of Hematology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi – 110029. India

4 Professor and Head, Department of Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi – 110029. India

5 Department of Biochemistry, All India Institute of Medical Sciences, Phulwarisharif, Patna – 801505 . India.

Abstract

 
Background: This study was performed to investigate any association between cellular cholesterol homeostasis and chronic lymphocytic leukemia (CLL). CLL is characterized primarily by an abnormal accumulation of neoplastic B cells in the blood, bone marrow, lymph nodes and spleen. Methods: Men aged >50 years participated in this study. Enzyme-based plasma lipid profile estimations, peripheral blood lymphocyte isolation, lysate preparations, SDS-PAGE, western blotting, dil-LDL uptake and ultracentrifugation were employed. Results: Our study demonstrated hypocholesterolemia in lymphocytic leukemia in addition to hyper-expression of LDLRs in leukemic lymphocytes. Breakdown of intracellular cholesterol homeostasis and failure to maintain the feedback mechanism normally processed by the transcription factor SREBP-2 in the cytoplasm was apparent. The presence of cholesterol in the nucleus was noted in leukemic lymphocytes. A comparison of cholesterol homeostasis between healthy controls and CLL subjects showed that cholesterol may contribute to lymphocytic leukemia. While plasma cholesterol levels decreased (p < 0.0005), hyper-expression of LDLR (p=0.0001), SREBP-2 (transcription factor of LDLR) (p=0.0001) and PBR (nuclear cholesterol channel protein) (p=0.016) was observed in lymphocytes isolated from CLL subjects in association with a significant increase in intracellular cholesterol in the nuclear (p=0.036) and cytoplasmic (p=0.004) compartments. Conclusion: This study provided insights into cholesterol homeostasis in CLL subjects regarding LDLR, SREBP-2 and PBR. Cholesterol may enter the nucleus through highly expressed PBR and may be involved in development of leukemia by influencing cell cycle mechanisms in the lymphocytes of CLL subjects.

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