Project description:Lenalidomide, an analogue of thalidomide, is immuno-modulatory drug and has been used for many types of cancer therapy. Recently, it has been reported that lenalidomide can enhance the function of NK cell during IL-2 response. However, molecular mechanism of action of lenalidomide in NK cells is unclear still. To investigate the modification by lenalidomide on NK cells, we conducted the analysis of gene expression on NK cells.
Project description:Genome-wide DNA accessibility maps of chromatin state in human CAR-T cells treated with lenalidomide in the presense or absense of Ag-specific restimulation
Project description:Lenalidomide, an IMiD® immunomodulatory agent used for the treatment of multiple myeloma (MM),is believed to target the stromal support, but its precise mechanism on the phenotype or the effector functions of macrophages is still unclear. To investigate the effect of lenalidomide on macrophages, M-CSF generated macrophages were treated with Lenalidomide and analyzed by RNA-seq.
Project description:Transcriptom-wide RNA expression profilng in human CAR-T cells treated with lenalidomide in the presense or absense of Ag-specific restimulation
Project description:Lenalidome is a drug especially effective in low risk myelodysplastic syndromes (MDS) with isolated 5q deletion. However, 25% of the patients did not respond. TP53 mutations have been described to play a role in the disease progression, and karyotypic complexity also has an important impact in the outcome. We selected 53 MDS patients with 5q deletion and treated with lenalidomide and we studied by the following techniques: conventional G-banding cytogenetics (CC), single nucleotide polymorphism arrays (SNP-A) and sequencing, in order to assess their impact on treatment response and disease progression. Low karyotypic complexity (by CC), a high baseline platelet count (>280x103/L) and TP53 unmutated gene status are associated with the achievement of hematological response (P=0.005, P=0.008 and P=0.057, respectively). In a multivariate model, the most important predictors for lenalidomide failure are karyotypic complexity (P=0.014) and a platelet count below 280x103/L (P=0.042). Additionally, none of the TP53 mutated cases achieved complete cytogenetics response. Nevertheless, inclusion of defects by SNP-A did not allow for a better separation of responders and non responders. These findings constitute a useful reference data to be considered before lenalidomide treatment enrollment.
Project description:Lenalidome is a drug especially effective in low risk myelodysplastic syndromes (MDS) with isolated 5q deletion. However, 25% of the patients did not respond. TP53 mutations have been described to play a role in the disease progression, and karyotypic complexity also has an important impact in the outcome. We selected 53 MDS patients with 5q deletion and treated with lenalidomide and we studied by the following techniques: conventional G-banding cytogenetics (CC), single nucleotide polymorphism arrays (SNP-A) and sequencing, in order to assess their impact on treatment response and disease progression. Low karyotypic complexity (by CC), a high baseline platelet count (>280x103/L) and TP53 unmutated gene status are associated with the achievement of hematological response (P=0.005, P=0.008 and P=0.057, respectively). In a multivariate model, the most important predictors for lenalidomide failure are karyotypic complexity (P=0.014) and a platelet count below 280x103/L (P=0.042). Additionally, none of the TP53 mutated cases achieved complete cytogenetics response. Nevertheless, inclusion of defects by SNP-A did not allow for a better separation of responders and non responders. These findings constitute a useful reference data to be considered before lenalidomide treatment enrollment. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from bone marrow or peripheral blood and, in some cases, also lymphocytes CD3 isolated from peripheral blood samples. Copy number analyses of Affymetrix 250K and 6.0 SNP arrays were performed for 53 MDS with 5q deletion samples. There are also 30 samples from lymphocytes CD3 isolated from peripheral blood, which were used as germ-line DNA (control).
Project description:To clarify the machinery how lenalidomide inhibit proplatelet formation of megakaryocytes, we performed transcriptome analysis of megakaryocytes derived from human hematopoietic stem/progenitor cells in the liquid culture system with or without lenalidomide. Differentially expressed genes were comprehensively evaluated by gene set enrichment analysis. Untreated megakaryocytes showed the estradiol-responded gene expression signatures, whereas the lenalidomide-treated megakaryocytes did not. Furthermore, we performed a rescue strategy with exogenous estradiol, confirming that lenalidomide-induced inhibition of proplatelet formation should be due to the deficiency of endogenous estradiol action in megakaryocytes.