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Published on: June 16, 2017
Changes associated with lenalidomide treatment in the gene expression profiles of patients with del(5q)
Monika Belickova1, Jaroslav Cermak, Michaela Dostalova Merkerova
1Institute of Hematology and Blood Transfusion, Prague, Czech Republic. monika.belickova@uhkt.cz
Unlabelled:
We used microarray profiling to investigate the direct effects of lenalidomide on gene expression in isolated CD14(+) monocytes from 6 patients with del(5q). Our data demonstrate that changes in genes involved the tumor necrosis factor (TNF) signaling pathway and the bone marrow stroma, suggesting that treatment with lenalidomide may help restore the damaged niche and suppress the TNF signaling pathway.
Background:
Lenalidomide is an effective treatment for patients with del(5q) and myelodysplastic syndrome (MDS) The exact mechanism of lenalidomide function and its impact on the prognosis of patients is not known exactly.
Materials And Methods:
We used gene expression profiling to study the effect of lenalidomide therapy in peripheral blood CD14(+) monocytes of 6 patients with del(5q) and MDS.
Results:
After lenalidomide treatment, genes involved in the tumor necrosis factor (TNF) signaling pathway that were upregulated in the patients before treatment decreased to the healthy control baseline expression level. This change in gene expression, in conjunction with increased expression of repressed genes that affect the stem cell niche (ie, CXCR4 and CRTAP), may exert a positive effect on treated patients. In contrast, we found that increased expression of the ARPC1B gene may have a negative impact on the stability of patient remission.
Conclusion:
The observed changes in gene expression described here may contribute to the identification of pathways that are affected by lenalidomide, which may help to explain the effects of this drug.
Insights
Lenalidomide treatment for del(5q) myelodysplastic syndrome (MDS) downregulates tumor necrosis factor (TNF) signaling and upregulates stem cell niche genes. These gene expression changes may explain lenalidomide
Area of Science:
- Hematology
- Molecular Biology
- Genomics
Background:
- Lenalidomide is an effective treatment for del(5q) myelodysplastic syndrome (MDS).
- The precise mechanism of lenalidomide's action and its prognostic impact remain unclear.
Purpose of the Study:
- To investigate the direct effects of lenalidomide on gene expression in CD14(+) monocytes from patients with del(5q) MDS.
- To elucidate the molecular pathways influenced by lenalidomide therapy.
Main Methods:
- Microarray gene expression profiling was employed.
- Analysis was performed on isolated CD14(+) monocytes from 6 patients with del(5q) MDS before and after lenalidomide treatment.
Main Results:
- Lenalidomide treatment led to decreased expression of upregulated tumor necrosis factor (TNF) signaling pathway genes to baseline levels.
- Expression of stem cell niche-related genes (CXCR4, CRTAP) increased post-treatment.
- Increased ARPC1B gene expression was observed, potentially impacting remission stability.
Conclusions:
- Observed gene expression changes provide insights into lenalidomide's mechanism of action in del(5q) MDS.
- Lenalidomide may restore the bone marrow niche and suppress TNF signaling.
- Further research into ARPC1B's role is warranted for understanding remission stability.
