Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA184017 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Bone marrow micro-environment mediated drug resistance in Acute promyelocytic leukemia
| PRJNA296065 | ENA
Project description:In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA)
2009-10-06 | GSE18397 | GEO
Project description:Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) chromosome translocation that generates the promyelocytic leukemia/retinoic acid receptor-α (PML/RARα) fusion gene. However, the mechanism underlying PML/RARα mediated transcriptional dysregulation remain unclear. Here, we performed the transcription profiling of BRD4 in NB4, an APL patient-derived cell line.
2024-07-30 | GSE232294 | 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:The differentiation of leukemia stem cells (LSCs) is generally regarded as a one-way alterative process to self-renewal. However, how differentiation impacts LSC stemness has largely been unexplored. Here we show that before reaching terminal differentiation (TD), apical LSCs of mouse acute promyelocytic leukemia passed through a partial differentiation (PD) stage, wherein the leukemia cells re-initiated leukemia via de-differentiation albeit at a reduced rate. Notably, while retinoic acid (RA) preferentially drove the transition of LSC to PD, monocytic Irf8 skewed PD cells to terminal maturation over de-differentiation and/or expansion. Remarkably, the combined use of RA and Irf8 induction depleted the total leukemogenic potential, which indicates that discrete stage- or lineage-specific mechanisms elaborate a step-wise LSC differentiation. We used microarrays to detail the global programme of gene expression indicating the molecular mechanisms unerlying the the process of LSC step-wise differentiation. Retroviral GFP-labled mouse APL cells (bone marrow sample) were repopulated in vivo through transplantation into syngenic recipients. At the proper time points, the GFP positive APL bone marrow cells were collected and sorted for UNSC, UNPD and UNTD samples through FACS. RA-PD and RA-TD cells were sorted from bone marrow tissue treated with ATRA (all trans retinoic acid) for 5 days. The freshly isolated samples were then lysed for RNA extration. Each sample had two biological replicates.
2014-05-01 | E-GEOD-46094 | biostudies-arrayexpress
Project description:Co-targeting the plasticity and heterogeneity of cancer is fundamental to achieve and maintain complete remission (CR). We exploited murine models of acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia driven by the promyelocytic leukemia/retinoic acid receptor (PML-RARα) oncofusion protein, which recruits histone deacetylase (HDAC)-containing complexes. We investigated the effect of two HDAC inhibitors: valproic acid (VPA), and SAHA/vorinostat with all-trans retinoic acid (ATRA), on the bulk cells and LICs of two APLs with different LIC frequencies. VPA and SAHA selectively target the bulk APL cells and LICs respectively. VPA+SAHA+ATRA combination induced CR in an APL model with lower LIC frequency.
2023-02-08 | GSE196379 | GEO
Project description:Here we report a new fusion gene, STRN3-RARA, in acute promyelocytic leukemia (APL). It cooperates with UTX deficiency to drive full-blown APL in mice. Although STRN3-RARA leukemia quickly relapses after all-trans retinoic acid treatment, it can be restrained by cepharanthine.
2024-04-23 | GSE224816 | GEO
Project description:The origin of aberrant DNA methylation in cancer remains largely unknown. In this study, we elucidated the DNA methylome in primary Acute Promyelocytic Leukemia (APL) and the role of PML-RARa in establishing these patterns. APL patients showed increased genome-wide DNA methylation with higher variability than healthy CD34+ cells, promyelocytes and remission bone marrow. A core set of differentially methylated regions in APL was identified. Age at diagnosis, Sanz score and Flt3-mutation status characterized methylation subtypes. Transcription factor binding sites, e.g. c-myc binding sites were associated with low methylation. SUZ12 and REST binding sites identified in embryonic stem cells were, however, preferentially DNA hypermethylated in APL. Unexpectedly, PML-RARa binding sites were also protected from aberrant DNA methylation in APL. In line, myeloid cells from pre-leukemic PML-RARa knock-in mice did not show altered DNA methylation and expression of PML-RARa in hematopoietic progenitor cells prevented differentiation without affecting DNA methylation. ATRA treatment of APL blasts did also not result in DNA methylation changes. These results suggest that aberrant DNA methylation is associated with leukemia phenotype but not required for PML-RARa-mediated initiation of leukemogenesis. Bisulphite converted DNA from the 10 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2012-11-08 | E-GEOD-42118 | biostudies-arrayexpress
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:Here we report a novel fusion gene, RUNX1-RARA, in acute promyelocytic leukemia (APL). RUNX1-RARA triggers APL genesis by mediating transcriptional repression of target genes, and it can be potently restrained by all-trans retinoic acid treatment.
2024-09-28 | GSE277794 | GEO