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Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Over-expression of the functional interleukin-11 alpha receptor in the development of B-cell chronic lymphocytic
A Tsimanis1, L Shvidel, A Klepfish
1Department of Hematology, Kaplan Medical Center, POB 1, Rehovot, 76100, Israel. Yehudats@netvision.net.il
Insights
The IL-11/IL-11R alpha system is constitutively expressed in B-chronic lymphocytic leukemia (B-CLL) cells. This system activates B-CLL cells, suggesting a key role in the disease pathogenesis.
Area of Science:
- Immunology
- Hematology
- Molecular Biology
Background:
- Cytokines are implicated in the pathogenesis of B-chronic lymphocytic leukemia (B-CLL).
- The specific role of IL-11 and its receptor (IL-11R alpha) in B-CLL requires further elucidation.
Purpose of the Study:
- To investigate the expression and function of IL-11 and IL-11R alpha in B-CLL cells.
- To determine the impact of IL-11 on B-CLL cell activation, proliferation, and survival.
Main Methods:
- Reverse-transcriptase polymerase chain reaction (RT-PCR) for gene expression analysis.
- FACS analysis and immunofluorescence for protein expression and localization.
- Treatment of B-CLL cells with recombinant human IL-11 (rhIL-11) and dexamethasone.
Main Results:
- Constitutive expression of IL-11 and IL-11R alpha was observed in B-CLL cells.
- IL-11R alpha expression was significantly higher in B-CLL cells compared to normal peripheral blood lymphocytes (PBL).
- rhIL-11 activated B-CLL cells, inducing morphological changes and increasing cell number and size, without affecting short-term survival or resistance to dexamethasone.
Conclusions:
- The IL-11/IL-11R alpha system is constitutively expressed in B-CLL cells.
- IL-11 plays a role in activating malignant B-CLL cells.
- These findings suggest a critical involvement of the IL-11/IL-11R alpha pathway in B-CLL pathogenesis.
Abstract:
Several cytokines have been found to play a role in the pathogenesis of B-CLL. In the present study using reverse-transcriptase polymerase chain reaction (RT-PCR), FACS analysis and immunofluorescence we have shown the constitutive expression of IL-11 and IL-11R alpha in B-chronic lymphocytic leukemia (B-CLL). The expression level of IL-11R alpha in B-CLL cells is much higher than in PBL of normal donors. Recombinant human IL-11 (rhIL-11) activates B-CLL cells, leading to morphologic alterations of the cells and increase in cell number and size. Short-term cultivation in the presence of rhIL-11 did not lead to quantitative changes in the ratio of the living vs apoptotic and dead cells. However, in contrast to rhIL-6, pretreatment with rhIL-11, did not cause B-CLL cells to be resistant to the action of dexamethasone. These data suggest an essential role for the IL-11/IL11 R alpha system in the pathogenesis of the malignant B-CLL cells.
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