Lipid-load in leukemia cells: studying the impact of environmental and demographic parameters

Lipid-load in leukemia cells: studying the impact of environmental and demographic parameters

Previous works indicate that cholesterol metabolism is deregulated in several types of malignancies including leukemia. Different types of cancer cells are previously shown to accumulate intracellular cholesterol. However, the data on intracellular cholesterol levels in leukemia cells provide contradictory evidence. Various previous works indicate either increase, decrease or no difference in total cellular cholesterol levels between leukemia cells and healthy peripheral blood mononuclear cells (PBMCs). We are studying in detail the lipid-load in leukemia cells and the associated factors. Our previous work indicates that PBMCs from AML and ALL patients display significantly lower intracellular levels of total cholesterol in comparison to PBMCs from the healthy subjects. Consistent with the patient data ALL and AML cell lines also display significantly lower cellular levels of total cholesterol. We confirmed this observation using multiple methodological approaches. Both ALL and AML cell lines also display significantly lower levels of free cholesterol and cholesteryl ester contents in comparison to normal hematopoietic cells. We observed that more than 90% of the total cholesterol in leukemia cells as well as in normal PBMCs was present in the form of cholesteryl esters. It was also observed that the lower levels of cholesterol in leukemia cells are not affected by exogenous cholesterol availability. Currently, we are assessing the impact of demographic and dietetic factors on lipid deposition in leukemia cells.

Acute leukemia cells display lower levels of intracellular cholesterol in comparison to mononuclear cells isolated from peripheral blood of healthy donors. (a)  Intracellular levels of total cholesterol in mononuclear cells isolated from peripheral blood of healthy subjects and acute lymphocytic leukemia patients. Significance was determined by unpaired t-test. **Significant difference ( p< 0.01).  (b)  Intracellular levels of total cholesterol in mononuclear cells isolated from peripheral blood of healthy subjects and acute myeloid leukemia patients. Significance was determined by unpaired t-test. **Significant difference (p < 0.01).  (c) Intracellular levels of total cholesterol in ALL cell lines, AML cell lines, peripheral blood mononuclear cells (PBMCs) (freshly isolated or stimulated with PHA for 48 hours) from healthy donors (HD). *Significant difference (P<0.01) comparing different acute leukemia cell lines with freshly isolated PBMCs from healthy donors. #Significant difference (P<0.01) comparing different acute leukemia cell lines with PHA stimulated PBMCs from healthy donors. αSignificant difference (P<0.01) comparing freshly isolated PBMCs with PHA stimulated PBMCs from healthy donors. (d)and (e) Relativeintracellular levels of free cholesterol and cholesteryl esters, respectively,  in ALL cell lines, AML cell lines andPHA stimulated PBMCs (48 hours) from healthy donors (S1 , S2 and S3). (f) Representation of free cholesterol and cholesteryl ester as a percentage of total cholesterol in ALL cell lines, AML cell lines and PHA stimulated PBMCs (48 hours) from healthy donors. (g) Expression of HMGCR in cell extracts from ALL cell lines, AML cell lines and PHA stimulated PBMCs (48 hours) from healthy donors (S1 and S2). Arbitrary ELISA units (AEU) were customized by running a parallel standard curve using different dilutions of HepG2 cell extracts.

Related publications from our research group

  1. Usman H, Ameer F, Munir R, Iqbal A, Zaid M, Hasnain S, Scandiuzzi L, Zaidi N: Leukemia cells display lower levels of intracellular cholesterol irrespective of the exogenous cholesterol availability. Clin Chim Acta 2016, 457:12-17. 
Level Student’s Name Thesis Title Year
PhD Hina Usman Regulation of plasma and cellular cholesterol levels in acute myeloid and lymphocytic leukemia Thesis submitted in 2019
Fatima Ameer Factors affecting lipid and lipidomic profile of malignant and non-malignant hematopoietic cells. Work in progress
M.Phil. Areeb Iqbal Cholesterol Homeostasis in Acute Leukaemia Patients: Studying the Intra- and Extracellular Cholesterol Content 2014-15
Undergraduate Shajan Qaisirani Lipid homeostasis in peripheral blood mononuclear cells 2015-16