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

Document Type : Research Articles


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.


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.


Main Subjects

Volume 18, Issue 1
January 2017
Pages 23-30
  • Receive Date: 23 August 2016
  • Revise Date: 26 December 2016
  • Accept Date: 16 February 2017
  • First Publish Date: 16 February 2017