Cdx2 driven acute myeloid leukemia is sensitive to therapy used in myeloid disease [RNASeq_Cdx2_AML_Azacitidine]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA552225 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9624780.fastq.gz | Fastqsanger.gz | |||
| SRR9624781.fastq.gz | Fastqsanger.gz | |||
| SRR9624782.fastq.gz | Fastqsanger.gz | |||
| SRR9624783.fastq.gz | Fastqsanger.gz | |||
| SRR9624784.fastq.gz | Fastqsanger.gz |
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Project description:The caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs . Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations.
2019-09-30 | GSE133680 | GEO
Project description:A) Chromatins were prepared from Cdx2-inducible ES cells cultured for 48 - 60 hours in the Dox+ and Dox- conditions. Chromatin immunoprecipitation (ChIP) was carried out by using anti-FLAG M2 affinity gel. ChIP product was tested by Western blotting using anti-FLAG antibody. Nuclear extract from ES cells cultured for 48 - 60 hours in Dox+ and Dox- condition was used for the Western blot. B) CDX2 ChIP-Seq peaks in the Hoxa7 gene region. UCSC Mouse Mm9 browser view of Hoxa7 gene locus after mapping CDX2 ChIP-Seq tags locations in the wiggle format. CDX2 ChIP-Seq peaks are shown in red color. C) Cdx2 ChIP-Seq result was verified by qPCR. Target genes were indicated in (G). Primers flanking a promoter region of Hbb-b1 and Pou5f1 as well as a gene desert region in chromosome 3 were used as negative controls. Primers flanking of Actb gene promoter were used for normalization. The relative enrichment of CDX2 binding was indicated as fold change. (D) CDX2-binding motifs identified with CisFinder using 200 bp sequences centered at ChIP sites. (F) Potential CDX2-direct target genes based on ChIP-Seq and the alteration of expression by Cdx2-overexpression. (G) Identification of CDX2 target genes by combining information on binding sites with gene expression response to Cdx2 over-expression
2009-10-01 | GSE14586 | GEO
Project description:Background: Lack of expression of the transcription factor CDX2 identifies a subset of poorly differentiated colorectal cancers (CRCs) that are associated with lower overall (OS) and disease-free (DFS) survival, independent of ethnicity, MSI status, or stage. CDX2 expression lowers risk of death and disease recurrence by ~50%. Induction of CDX2 as a therapeutic strategy is yet to be implemented in clinical practice. Methods: We used a novel network-based computational model to identify and prioritize therapeutic targets that can robustly augment CDX2 expression and, consequently, differentiation. The top candidate with available clinical-grade pharmacophore was tested for efficacy in 3 models: CRC lines in vitro, xenografts in mice, and in prospective cohorts of CRC patient-derived organoids (PDOs; n = 23). Results: Our network-derived gene clusters reliably classified healthy and CRC tissues in diverse publicly available gene expression datasets (>10,000 human and >250 mouse samples). The target showed potent anti-cancer activity, induced crypt differentiation signatures in all models tested, and shifted the network in predictable ways. Effective pairing of therapy (IC50 of the target) and CDX2 expression (companion biomarker) was confirmed in an independent cohort of CRC PDOs. A multivariate analysis revealed KRAS mutation and high-CDX2 as key determinants of resistance to the target. Conclusions: Induction of CDX2 expression by the target augments differentiation and shows potent anti-cancer effect on CRCs that lack CDX2 expression. This benefit of drug-biomarker pairing should be considered for confirmatory studies in randomized clinical trials.
2025-09-23 | GSE237625 | GEO
Project description:A) Chromatins were prepared from Cdx2-inducible ES cells cultured for 48 - 60 hours in the Dox+ and Dox- conditions. Chromatin immunoprecipitation (ChIP) was carried out by using anti-FLAG M2 affinity gel. ChIP product was tested by Western blotting using anti-FLAG antibody. Nuclear extract from ES cells cultured for 48 - 60 hours in Dox+ and Dox- condition was used for the Western blot. B) CDX2 ChIP-Seq peaks in the Hoxa7 gene region. UCSC Mouse Mm9 browser view of Hoxa7 gene locus after mapping CDX2 ChIP-Seq tags locations in the wiggle format. CDX2 ChIP-Seq peaks are shown in red color. C) Cdx2 ChIP-Seq result was verified by qPCR. Target genes were indicated in (G). Primers flanking a promoter region of Hbb-b1 and Pou5f1 as well as a gene desert region in chromosome 3 were used as negative controls. Primers flanking of Actb gene promoter were used for normalization. The relative enrichment of CDX2 binding was indicated as fold change. (D) CDX2-binding motifs identified with CisFinder using 200 bp sequences centered at ChIP sites. (F) Potential CDX2-direct target genes based on ChIP-Seq and the alteration of expression by Cdx2-overexpression. (G) Identification of CDX2 target genes by combining information on binding sites with gene expression response to Cdx2 over-expression Chromatin IP against CDX2-Flag fusion protein. MC1 ES cells were genetically modified for ROSA26 locus to have Tet-Off expression cassette for C-terminal FLAG tagged Cdx2. The peaks are obtained from the Eland Multi Alignment file. The number of tags in peaks was compared with the number of tags in the control sample for the same region corrected by the total coverage of tags. See supplemental file of the paper for details.
2009-10-01 | E-GEOD-14586 | biostudies-arrayexpress
Project description:Background: Lack of expression of the transcription factor CDX2 identifies a subset of poorly differentiated colorectal cancers (CRCs) that are associated with lower overall (OS) and disease-free (DFS) survival, independent of ethnicity, MSI status, or stage. CDX2 expression lowers risk of death and disease recurrence by ~50%. Induction of CDX2 as a therapeutic strategy is yet to be implemented in clinical practice. Methods: We used a novel network-based computational model to identify and prioritize therapeutic targets that can robustly augment CDX2 expression and, consequently, differentiation. The top candidate with available clinical-grade pharmacophore was tested for efficacy in 3 models: CRC lines in vitro, xenografts in mice, and in prospective cohorts of CRC patient-derived organoids (PDOs; n = 23). Results: Our network-derived gene clusters reliably classified healthy and CRC tissues in diverse publicly available gene expression datasets (>10,000 human and >250 mouse samples). The target showed potent anti-cancer activity, induced crypt differentiation signatures in all models tested, and shifted the network in predictable ways. Effective pairing of therapy (IC50 of the target) and CDX2 expression (companion biomarker) was confirmed in an independent cohort of CRC PDOs. A multivariate analysis revealed KRAS mutation and high-CDX2 as key determinants of resistance to the target. Conclusions: Induction of CDX2 expression by the target augments differentiation and shows potent anti-cancer effect on CRCs that lack CDX2 expression. This benefit of drug-biomarker pairing should be considered for confirmatory studies in randomized clinical trials.
2025-09-23 | GSE237624 | GEO
Project description:Background: Lack of expression of the transcription factor CDX2 identifies a subset of poorly differentiated colorectal cancers (CRCs) that are associated with lower overall (OS) and disease-free (DFS) survival, independent of ethnicity, MSI status, or stage. CDX2 expression lowers risk of death and disease recurrence by ~50%. Induction of CDX2 as a therapeutic strategy is yet to be implemented in clinical practice. Methods: We used a novel network-based computational model to identify and prioritize therapeutic targets that can robustly augment CDX2 expression and, consequently, differentiation. The top candidate with available clinical-grade pharmacophore was tested for efficacy in 3 models: CRC lines in vitro, xenografts in mice, and in prospective cohorts of CRC patient-derived organoids (PDOs; n = 23). Results: Our network-derived gene clusters reliably classified healthy and CRC tissues in diverse publicly available gene expression datasets (>10,000 human and >250 mouse samples). The target showed potent anti-cancer activity, induced crypt differentiation signatures in all models tested, and shifted the network in predictable ways. Effective pairing of therapy (IC50 of the target) and CDX2 expression (companion biomarker) was confirmed in an independent cohort of CRC PDOs. A multivariate analysis revealed KRAS mutation and high-CDX2 as key determinants of resistance to the target. Conclusions: Induction of CDX2 expression by the target augments differentiation and shows potent anti-cancer effect on CRCs that lack CDX2 expression. This benefit of drug-biomarker pairing should be considered for confirmatory studies in randomized clinical trials.
2025-09-23 | GSE237623 | GEO
Project description:Aberrant expression of the homeodomain transcription factor CDX2 occurs in most cases of acute myeloid leukemia (AML) and promotes leukemogenesis, making CDX2, in principle, an attractive therapeutic target. Conversely, CDX2 acts as a tumor suppressor in colonic epithelium. The effectors mediating the leukemogenic activity of CDX2 and the mechanism underlying its context-dependent properties are poorly characterized, and strategies for interfering with CDX2 function in AML remain elusive. We report data implicating repression of the transcription factor KLF4 as important for the oncogenic activity of CDX2, and demonstrate that CDX2 differentially regulates KLF4 in AML versus colon cancer cells through a mechanism that involves tissue-specific patterns of promoter binding and epigenetic modifications. Furthermore, we identified deregulation of the PPARγ signaling pathway as a feature of AML expressing CDX2, and observed that PPARγ agonists derepress KLF4 and are preferentially toxic to CDX2-positive leukemic cells. These data delineate transcriptional programs associated with CDX2 expression in hematopoietic cells; provide insight into the antagonistic duality of CDX2 function in AML versus colon cancer; and suggest reactivation of KLF4 expression, through modulation of PPARγ signaling, as a new therapeutic modality in a large proportion of AML patients.
2012-12-21 | GSE40939 | GEO
Project description:The caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs. Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations.
2019-09-30 | GSE133679 | GEO
Project description:The caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs . Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations.
2019-09-30 | GSE133828 | GEO
Project description:The caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs. Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations.
2020-03-09 | GSE146598 | GEO