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Updated: May 2, 2026
Culture of myeloid dendritic cells from bone marrow precursors
Published on: July 25, 2008
Monocyte-derived dendritic cells from chronic myeloid leukaemia have abnormal maturation and cytoskeletal function
Sarah Brown1, Claire V Hutchinson, Mark Aspinall-O'Dea
1Pharmacy Department, University of Wolverhampton, Wolverhampton, UK.
Insights
In chronic myeloid leukemia, BCR-ABL1 disrupts normal ABL1 signaling in dendritic cells (DCs). This leads to defective DC function, impacting their therapeutic potential.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Dendritic cells (DCs) in chronic myeloid leukemia (CML) originate from BCR/ABL1-expressing monocytes.
- These CML-derived DCs exhibit functional defects, limiting their therapeutic applications.
- Normal DC activation and maturation rely on ABL1-dependent signaling pathways.
Purpose of the Study:
- To investigate how the BCR/ABL1 molecule affects ABL1 signaling in CML DCs.
- To determine if disrupted ABL1 pathways contribute to the functional defects observed in CML DCs.
Main Methods:
- In vitro culture of clinical samples from CML patients and healthy individuals.
- Microscopic and biochemical techniques were utilized.
- Phosphoproteomic analysis was employed for comparative characterization.
Main Results:
- ABL1 exhibited altered intracellular localization in CML DCs, found in the perinuclear region.
- BCR/ABL1 protein and CRKL adapter protein co-distributed with ABL1 in the perinuclear area.
- Defective ABL1-dependent maturation signals and ABL1 dislocation from the F-actin cytoskeleton were observed.
Conclusions:
- Altered ABL1 localization and signaling disrupt normal DC maturation in CML.
- Abnormal ABL1-dependent signals contribute to the functional deficits of CML DCs.
- These findings provide insights into CML pathogenesis and potential therapeutic strategies targeting DC function.
Objectives:
Mature dendritic cells (DCs) may be derived from the BCR/ABL1 expressing monocytes in chronic myeloid leukaemia. These cells have potential therapeutic applications, but are recognised to have defective function. In normal DCs, activation and maturation depend on ABL1 dependent signals. We therefore tested the hypothesis that in the DCs of chronic myeloid leukaemia, the presence of the BCR/ABL1 molecule disrupts normal ABL1 signal pathways, and contributes to the observed functional defects of the cells.
Methods:
We employed in vitro culture of clinical samples, combining microscopic and biochemical techniques with a phosphoproteomic approach to compare and characterise DCs from normal individuals and chronic myeloid leukaemia patients.
Results And Conclusions:
We identified an altered intracellular localisation for ABL1 within DCs derived from the monocytes of chronic myeloid leukaemia. The protein was found in the perinuclear region co-distributed with the adapter-protein CRKL and the BCR/ABL1 protein. This altered distribution was associated with defective generation of ABL1-dependent maturation signals, and a dislocation of ABL1 from the F-actin cytoskeleton. We suggest that abnormal ABL1-dependent signals contribute to the recognised functional defects affecting chronic myeloid leukaemia DCs.
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