title: Cholesterol Homeostasis in Isolated Lymphocytes: a Differential Correlation Between Male Control and Chronic Lymphocytic Leukemia Subjects
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.
authors.affiliation: KLE University’s, J. N. Medical College, Belagavi, Karnataka- 590010. India. Email:nc1_chandra@hotmail.com
authors.forename: Shrimanjunath
authors.initials: Sh
authors.lastname: Sankanagoudar
authors.forename: Govind
authors.initials: G
authors.lastname: Singh
authors.forename: Manaranjan
authors.initials: M
authors.lastname: Mahapatra
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
authors.forename: Nimai Chand
authors.initials: NCh
authors.lastname: Chandra
keywords: LDL; LDL receptor; PBR; nuclear cholesterol; chronic lymphocytic leukemia