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Updated: Jun 29, 2025
11:39
Subcellular Fractionation of Primary Chronic Lymphocytic Leukemia Cells to Monitor Nuclear/Cytoplasmic Protein Trafficking
Published on: October 23, 2019
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Analysis of Primary Chronic Lymphocytic Leukemia Cells' Signaling Pathways.
Josipa Skelin1, Maja Matulić2, Lidija Milković1
1Ruđer Bošković Institute, 10000 Zagreb, Croatia.
Biomedicines
|March 28, 2024
Summary
Chronic lymphocytic leukemia (CLL) outcomes vary based on active genes and pathways. NOTCH1 pathway activation in vitro increases CLL cell apoptosis, even with high BCL2 expression.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Chronic lymphocytic leukemia (CLL) is a B-cell malignancy with heterogeneous clinical outcomes.
- Disease progression is linked to specific genes and signaling pathways within the malignant clone.
- Key pathways implicated include NOTCH1, Ikaros family genes, BCL2, and NF-κB, promoting leukemic cell survival and proliferation.
Purpose of the Study:
- To investigate the gene and protein expression of NOTCH1, DELTEX1, HES1, and AIOLOS in CLL cells.
- To analyze the expression of BCL2 and microRNAs (miRNAs) in relation to these genes.
- To determine if NOTCH pathway activation impacts CLL cell apoptosis.
Main Methods:
- Analysis of gene and protein expression in primary CLL cells from peripheral blood lymphocytes (PBLs) and bone marrow (BM).
- Quantitative assessment of NOTCH1, DELTEX1, HES1, AIOLOS, BCL2, and specific miRNAs (miR-15a, miR-181, miR-146, miR-155).
- In vitro experiments to study the effect of NOTCH pathway activation on CLL cell apoptosis.
Main Results:
- BCL2 and AIOLOS showed high expression in all CLL samples, with AIOLOS higher in PBLs than BM.
- NOTCH1 activation was found to be higher in the bone marrow.
- Decreased expression of miR-15a, miR-181, miR-146 and increased expression of miR-155 were observed in most samples.
- In vitro NOTCH pathway activation sensitized CLL cells to apoptosis, irrespective of high BCL2 levels.
Conclusions:
- CLL exhibits distinct molecular profiles in peripheral blood and bone marrow.
- NOTCH pathway activation plays a significant role in CLL pathogenesis and may represent a therapeutic target.
- Modulating the NOTCH pathway could overcome resistance to apoptosis mediated by BCL2 in CLL.
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