2024-03-29T09:35:59Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1775882020-01-28T12:03:14Zcom_10261_112com_10261_1col_10261_491
Changes in the gene expression profile of multiple myeloma cell line in response to immunomodulatory (IMIDs) drugs: MYB gen target
Fernández-Lázaro, Diego
Fernández-Lázaro, César Ignacio
San-Segundo, Laura
Ocio, Enrique M.
Asociación Española Contra el Cáncer
Ministerio de Ciencia y Tecnología (España)
Instituto de Salud Carlos III
Multiple myeloma
Immunomodulatory drugs
Gene expression
Resumen del trabajo presentado al 5th Symposium on Biomedical Research: "Advances and Perspectives In Pharmacology, Drug Toxicity and Pharmacogenetics", celebrado en Madrid del 15 al 16 de marzo de 2018.
[Introduction]: The immunomodulatory drug (IMiD) thalidomide and its structural analogs lenalidomide and pomalidomide are highly used to treat multiple myeloma (MM), however the molecular mechanism of IMiDs’ action is not well-established. There before, we performed gene expression profiling analyses using microarray technologies to determine changes in genes involved in cellular biological pathways of MM induced by IMiDs in monotherapy.
[Material and Methods]: We used MM1S cell line with concentrations of lenalidomide (1μM) and pomalidomide (100nM) in six-well plates for 1 and 5 days at 37 °C. After treatment, MM1S cells were evaluated by flow cytometry using Annexin-V and propidium iodide after selective labelling of plasma cells with CD38 and CD138 antibodies. The samples were analyzed using Affimetrix Gene-chip Expression Arrays. The absolute expression values for each probe were calculated using the MAS
5.0 software. The comparative analyzes were carried out using the Dchip program, the SAM algorithm, and the Ingenuity Pathway Analysis software. Expression changes were deemed significant if they were ±2-fold. Ingenuity Pathway Analysis was used to identify the most relevant biological mechanisms, pathways, and functional categories in the data set of genes selected by statistical analysis.
[Results]: After 1-day, in vitro treatment with lenalidomide (1μM), with 5-7% apoptosis, significantly deregulated 10 genes whereas treatment with pomalidomide (100nM), with 8-10% apoptosis, deregulated 19 genes. Among these genes, 6 genes were exclusively deregulated by lenalidomide, 15 were deregulated by pomalidomide, and 4 genes were regulated by both lenalidomide and pomalidomide. After 5-days, in vitro treatment with lenalidomide (1μM), with 20-22% apoptosis,
significantly deregulated 39 genes whereas treatment with pomalidomide (100nM), with 25-27% apoptosis, deregulated 359 genes. Among these genes, 8 genes were exclusively deregulated by lenalidomide, 328 were deregulated by pomalidomide, and 31 genes were regulated by both lenalidomide and pomalidomide. These dysregulated genes are involved in the most relevant biological pathways for MM.
[Conclusion]: We observed changes in the gene expression profile of MM cells after treatment with lenalidomide and pomalidomide, resulting pomalidomide with greater anti-MM effect. The under-expression of the MYB oncogene — regulator of transcription with an essential role in the control of the proliferation and differentiation of hematopoietic progenitor cells and their tumorigenesis— was commonly deregulated in both IMiDs lenalidomide and pomalidomide in monotherapy. Future studies may consider MYB as a new pharmacogenetic therapeutic target in MM.
2019-03-11T08:13:38Z
2019-03-11T08:13:38Z
2018
comunicación de congreso
5th Symposium on Biomedical Research (2018)
http://hdl.handle.net/10261/177588
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100006280
eng
Sí
closedAccess