Genome-wide expression profiling of acute promyelocytic leukemia NB4 cells treated with all-trans-retinoic acid
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE155779 | GEO | 2020/11/05
REPOSITORIES: GEO
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Project description:Acute promyelocytic leukemia (APL) is a hematological disease characterized by a balanced reciprocal translocation that leads to the synthesis of the oncogenic fusion protein PML-RARα. APL is mainly managed by a differentiation therapy based on the administration of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, therapy resistance, differentiation syndrome, and relapses require the development of new low-toxicity therapies based on the induction of blasts differentiation. Here, we performed a high-throughput gene expression profile of the ATRA-resistant acute promyelocytic leukemia (APL) cellline (aka R4) treated with a CHK1 inhibitor or DMSO as control.
2024-01-01 | GSE223329 | GEO
Project description:The aim of this study was to gain insight into the potential mechanism of resistance to arsenic trioxide (ATO). The gene expression profile of naive (NB4) (Acute promyelocytic leukemia (APL) cell line and one of its in house generated ATO resistant sub clone (NB4-VM-AsR1) was done using whole genome microarray and compared to generate the differential expression profile which will give insight into the mechanisms of ATO resistance in APL. Agilent one-color experiment,Organism: Human ,Agilent Whole Genome Human 4x44k (AMADID: 014850) , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442) naive versus arsenic trioxide resistant acute promyelocytic leukemia cell line NB4
2013-08-02 | E-GEOD-42031 | biostudies-arrayexpress
Project description:The aim of this study was to gain insight into the potential mechanism of resistance to arsenic trioxide (ATO). The gene expression profile of naive (NB4) (Acute promyelocytic leukemia (APL) cell line and one of its in house generated ATO resistant sub clone (NB4-VM-AsR1) was done using whole genome microarray and compared to generate the differential expression profile which will give insight into the mechanisms of ATO resistance in APL.
2013-08-02 | GSE42031 | GEO
Project description:To identify the top 20 up-regulated genes in NB4 TRIB3 shRNA cells in comparison with NB4 control shRNA cells, we examined the microarray gene expression profile of these groups above. Despite the fact that combined therapy of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) or chemotherapy dramatically improves the prognosis of patients with acute promyelocytic leukemia (APL), these regimens can cause systemic infections and secondary leukemias. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) associates positively with APL progression and therapeutic resistance. The elevated TRIB3 expression promotes APL by interacting with PML-RARa and suppressing its sumoylation, ubiquitylation and degradation. This represses PML nuclear body assembly, p53-mediated senescence, cell differentiation, and supports cellular self-renewal. Genetically inhibiting Trib3 expression or disturbing the TRIB3/PML-RARa interaction produces potent therapeutic efficacy against APL and has synergic anti-APL effects when used in combination with ATRA or ATO by promoting PML-RARa degradation and PML expression. Our study provides new insight into APL pathogenesis and a new therapeutic option against APL.
2017-05-12 | GSE95637 | GEO
Project description:We defined the RARα interactome in the MDA-MB453 breast cancer cell line genetically engineered to over-express an N-terminally tagged version of the nuclear retinoic acid receptor. Twenty eight nuclear proteins which interact with RARα and whose interaction is stimulated or reduced by the pan-RAR ligand, all-trans retinoic acid (ATRA) were identified. Given the potential significance of the S100A3 calcium-binding protein in the control of tumor progression, we focused our attention on this factor. Using the two models represented by the ATRA-sensitive SKBR3 and MCF7 breast cancer cell lines characterized by constitutive expression of S100A3 and RARα, we demonstrate that the endogenous forms of S100A3 and RARα interact in physiological conditions. The interaction of S100A3 with RARα is cell context independent and it is observed not only in breast cancer but also in acute promyelocytioc leukemia (APL) cells, characterized by expression of the RARα-derived PML-RARα oncogene, which is the product of the t(15:17) chromosomal translocation. S100A3 interacts directly and specifically with RARα and PML-RARα, being unable to bind other members of the RAR/RXR family of retinoid nuclear receptors. The interaction surface maps to the carboxyl-terminal region of the RARα ligand binding domain. Binding of S100A3 to RARα and PML-RARα controls the constitutive and ATRA-dependent degradation of the two receptors. Silencing of the S100A3 gene decreases the amounts of RARα in breast SK-BR-3 and lung A549 cancer cells, rendering them more refractory to the anti-proliferative action of ATRA. In SK-BR-3 cells, this effect is accompanied by a decrease in the lactogenic/differentiating action of ATRA. In APL-derived NB4 cells, S100A3 knock-down reduces the amounts of both RARα and PML-RARα. Contemporaneous down-regulation of the two receptors is associated with an increase in the basal and ATRA-induced expression of many granulocytic differentiation markers. Opposite on RARα and PML-RARα levels as well as ATRA induced differentiation markers are observed upon over-expression of S100A3 in NB4 cells.
2019-12-18 | PXD008761 | Pride
Project description:About 5-10% newly diagnosed and about 20-30% of relapsed acute promyelocytic leukemia (APL) patients will have disease recurrence after receiving currently accepted standards of care. While there are reports of micro-environment mediated drug resistance (EM-DR) in AML, there is no data on the effect of malignant promyelocyte and stromal interaction on Arsenic trioxide (ATO) induced apoptosis. We undertook a preliminary study to evaluate the role of EM-DR to ATO in APL. In direct co-culture (contact dependent system) of malignant promyelocyte with stromal cells, the stromal cells gave a significant protective effect against ATO at different concentrations used (1 to 8 μmol; NB4 (APL cell line) In a gene expression profiling comparing NB4 cells in co-culture with NB4 cells alone, 1846 genes were differentially regulated. On a preliminary analysis, we observed an up-regulation of various pathways such as adhesion (ITGB1, ITGB2, ITGB7, etc.), Cytokines (IL-6, IL-8, IL-18, CCL2, CCL10, etc.) Wnt signalling (Wnt5a, Wnt11, NFATC4, etc,) NF-kB pathway (ICAM1, BIRC2, BIRC3, XIAP1, etc.) in the leukemic cells. The NF-kB pathway has been validated using real time PCR which correlated with the genes being differentially regulated in NB4 cells co-cultured in stroma. Agilent one-color experiment,Organism: Homo sapiens ,Custom Agilent 8x60k Human Whole Genome Microarray Gene expression (AMADID: 039494) , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)
2016-09-01 | E-GEOD-73157 | biostudies-arrayexpress
Project description:About 5-10% newly diagnosed and about 20-30% of relapsed acute promyelocytic leukemia (APL) patients will have disease recurrence after receiving currently accepted standards of care. While there are reports of micro-environment mediated drug resistance (EM-DR) in AML, there is no data on the effect of malignant promyelocyte and stromal interaction on Arsenic trioxide (ATO) induced apoptosis. We undertook a preliminary study to evaluate the role of EM-DR to ATO in APL. In direct co-culture (contact dependent system) of malignant promyelocyte with stromal cells, the stromal cells gave a significant protective effect against ATO at different concentrations used (1 to 8 μmol; NB4 (APL cell line) In a gene expression profiling comparing NB4 cells in co-culture with NB4 cells alone, 1846 genes were differentially regulated. On a preliminary analysis, we observed an up-regulation of various pathways such as adhesion (ITGB1, ITGB2, ITGB7, etc.), Cytokines (IL-6, IL-8, IL-18, CCL2, CCL10, etc.) Wnt signalling (Wnt5a, Wnt11, NFATC4, etc,) NF-kB pathway (ICAM1, BIRC2, BIRC3, XIAP1, etc.) in the leukemic cells. The NF-kB pathway has been validated using real time PCR which correlated with the genes being differentially regulated in NB4 cells co-cultured in stroma.
2016-09-01 | GSE73157 | GEO
Project description:Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cells is transglutaminase 2 (TG2). RNAi-mediated stable silencing of TG2 in NB4 cells (TG2-KD NB4) coupled with whole genome microarray analysis revealed that TG2 is involved in the expression of a large number of ATRA-regulated genes. The affected genes participate in granulocyte functions and their silencing lead to reduced adhesive, migratory and phagocytic capacity of neutrophils and less superoxide production. The expression of genes related to cell cycle control also changed, suggesting that TG2 regulates myeloid cell differentiation. CC chemokines CCL2, 3, 22, 24 and cytokines IL1B and IL8 involved in the development of differentiation syndrome (DS) are expressed at significantly lower levels in TG2-KD NB4 cells than in wild-type NB4 cells upon ATRA treatment. Based on our results, we propose that reduced expression of TG2 in differentiating APL cells may suppress effector functions of neutrophil granulocytes and attenuate the ATRA-induced inflammatory phenotype of DS. We used microarrays to detail the global program of gene expression underlying ATRA-induced differentiation of TG2 knockout NB4 cells. TG2 knockout NB4 cells were differentiated for 48 and 72 hours in the presence of ATRA and their gene expression profiles were compared to the wild-type cells at the same time points. Undifferentiated wild-type and TG2 knockout NB4 cells were used as untreated controls. Three biological replicates each.
2010-12-01 | E-GEOD-23702 | biostudies-arrayexpress
Project description:HOTAIRM1 is a long intergenic non-coding RNA located in the human HOXA gene cluster, with gene expression highly specific for maturing myeloid cells, particularly during all-trans retinoic acid (ATRA) induction of granolopoiesis in NB4, a human t(15;17) acute promyelocytic leukemia (APL) cell line. We sought to assess the impact of HOTAIR knockdown on the global programme of gene expression underlying the granulocytic maturing process in NB4 cells. The knockdown of HOTAIRM1 resulted in a less differentiated expression profile in the NB4 cells after 4 days of ATRA-induced granulocytic differentiation, with retained expression of many otherwise ATRA-suppressed cell cycle and DNA replication genes, as well as abated induction of cell surface leukocyte activation and defense response genes.
2014-04-30 | GSE49516 | GEO
Project description:NB4 is an APL derived cell line, carrying the t(15;17) translocation and expressing the PML/RARa fusion protein. Still, an important question that remains to be addressed is whether PML/RARa target genes are transcriptionally suppressed in primary APL cells and re-activated in all-trans retinoic acid (ATRA) treated NB4 cells. Gene expression of NB4 cells treated with ATRA at different time points were analyzed.
2009-11-26 | GSE19201 | GEO