Effects of ATRA and ATO on expression profiles of APL cells in vivo
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE94017 | GEO | 2017/07/06
SECONDARY ACCESSION(S): PRJNA363061
REPOSITORIES: GEO
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Project description:Transcriptional profiling of human leukemia?HL-60 cells comparing ATRA treated HL-60 cells with ATRA plus ATO. Goal was to determine the effects of ATO on ATRA induced differentiation of HL-60 cells. Two-condition experiment, ATRA vs. ATRA plus ATO treated HL-60 cells.
2015-03-31 | E-GEOD-67420 | biostudies-arrayexpress
Project description:Transcriptional profiling of human leukemia HL-60 cells comparing ATRA treated HL-60 cells with ATRA plus ATO. Goal was to determine the effects of ATO on ATRA induced differentiation of HL-60 cells.
2015-03-31 | GSE67420 | GEO
Project description:ATRA is an active metabolite of vitamin A that is frequently used for the treatment of acute promyelocytic leukemia (APL) patients. Despite the success of this treatment, some APL patients are refractory or relapse. This emphasis the need for new therapeutic strategies aiming to improve the anti-cancer effect of ATRA. We and other have previously shown that autophagy is activated during ATRA-induced granulocytic differentiation of acute promyelocytic leukemia cells. Although the transcription effect of ATRA on autophagy has been well-documented, little is known on the post-transcription/ post-translational regulation autophagy in response to ATRA. Given the importance of calcium ions in the control of autophagy, we hypothesized that calcium ions are involved in the initiation of autophagy by ATRA in APL cells. We thus examined how ATRA regulate intracellular calcium and sense perturbation of Ca2+ responses to autophagy, differentiation and cell death in APL cells.
2021-11-24 | PXD026904 | Pride
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:Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination safely cures fatal acute promyelocytic leukemia, but the mechanisms underlying their action and synergy remain elusive. ATRA inhibits APL, breast and liver cancers by targeting isomerase Pin1, a master regulator of oncogenic signaling. Here we show that ATO targets Pin1 and cooperates with ATRA to exert potent anticancer activity. ATO inhibits and degrades Pin1, and suppresses its oncogenic function by noncovalent binding to Pin1’s active site. ATRA increases cellular ATO uptake through upregulating aquaporin-9. ATO and ATRA, at clinically safe doses, cooperatively ablate Pin1 to block numerous cancer-driving pathways and inhibit the growth of triple-negative breast cancer cells and tumor-initiating cells in cell and animal models including patient-derived orthotopic xenografts, similar to Pin1 CRISPR knockout, which is substantiated by comprehensive protein and microRNA analyses. Thus, synergistic Pin1 inhibition by ATO and ATRA offers an attractive approach to combating breast and other cancers.
2018-10-16 | PXD010224 | Pride
Project description:Acute promyelocytic leukaemia (APL) can be cured by the co-administration of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA). These small molecules relieve the differentiation blockade of the cancerous promyelocytes and trigger their maturation into functional neutrophils, which are physiologically primed for apoptosis. This normalization therapy uses low dose treatments and represents a compelling alternative to cytotoxic anticancer chemotherapy. However, the serendipitous discovery of this combination treatment prevented the establishment of methodologies to screen for novel combination treatments consisting of inducers of differentiation and other metallopharmaceuticals. Here, we present an experimental framework that enables interrogating the suitability, directionality and extent of normalization of novel combination treatments. Since the endpoint of this anticancer treatment is remodelling of cancer phenotypes, this approach requires a mechanism-driven understanding of the drug-induced cellular adaptions along the path to mature neutrophils. For this purpose, label-free quantification proteomics is used to probe the proteome changes upon differentiation and metal(-loid) treatment on the molecular level in a panel of ATRA-responsive and ATRA-non-responsive acute myeloid leukaemia (AML) cell lines, including APL. The induction of differentiation was confirmed by the up-regulation of canonical surface markers (e.g. CD11β) and validated by flow cytometry. The regulation of key transcription factors in this panel of AML cell lines reflects their position in the myeloid differentiation cascade (e.g. SPI1, GFI-1 and CEBPE). The additive/synergistic contributions of ATO to the combination treatment were thoroughly characterized and include changes in metabolic activities, as well as protein signatures related to management of reactive oxygen species and an integrated stress response. The latter two are also characteristic for the organoruthenium-based drug candidate plecstatin-1, which was recently shown to modulate the scaffold protein plectin. The combination of differentiation-induction and plecstatin-1 treatment featured a striking similarity in the responsiveness of the AML cancer cells compared to ATO+ATRA. It turned out to be at least equivalent in the regulation of key processes underlying normalization therapy in AML with granulocytic maturation. By exploiting response patterns of AML cancer cells induced by the ATO+ATRA combination treatment, this approach may allow identifying novel small molecule combinations, which may have the potential to achieve normalization and thus therapeutic benefit beyond APL.
2022-02-22 | PXD019619 | Pride
Project description:Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination safely cures fatal acute promyelocytic leukemia, but the mechanisms underlying their action and synergy remain elusive. ATRA inhibits APL, breast and liver cancers by targeting isomerase Pin1, a master regulator of oncogenic signaling. Here we show that ATO targets Pin1 and cooperates with ATRA to exert potent anticancer activity. ATO inhibits and degrades Pin1, and suppresses its oncogenic function by noncovalent binding to Pin1’s active site. ATRA increases cellular ATO uptake through upregulating aquaporin-9. ATO and ATRA, at clinically safe doses, cooperatively ablate Pin1 to block numerous cancer-driving pathways and inhibit the growth of triple-negative breast cancer cells and tumor-initiating cells in cell and animal models including patient-derived orthotopic xenografts, similar to Pin1 CRISPR knockout, which is substantiated by comprehensive protein and microRNA analyses. Thus, synergistic Pin1 inhibition by ATO and ATRA offers an attractive approach to combating breast and other cancers.
2018-08-20 | GSE116264 | GEO
Project description:Purpose: Treatment of acute promyelocytic leukemia (APL) with the retinoid, all trans retinoic acid (ATRA), along with standard chemotherapy has significantly improved survival compared to chemotherapy alone1. ATRA mediates its benefit in APL by overcoming the transcriptional block mediated by PML-RAR-alpha fusion oncoprotein, thereby, restoring expression of retinoid response genes2. The therapeutic benefits observed with ATRA treatment in APL have not been achieved in the other more common sub-types of acute myeloblastic leukemia (AML)3. This likely reflects the recruitment of histone deacetylase complexes by other recurrent chromosomal translocations in AML cells4. In this experiment, we evaluated if treatment of the AML cell line, OCI/AML-2, with the histone deacetylase inhibitor, valproic acid (VPA), would alter the expression of sub-sets of genes by itself or in conjunction with ATRA that have been shown to be modulated by ATRA in APL2. Keywords: other
2005-05-17 | GSE2668 | 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
Project description:In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA)
2009-10-06 | GSE18397 | GEO