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A cutting-edge approach unravels a novel role for CDK6 in leukemic progenitor cells

ABSTRACT: A cutting-edge approach unravels a novel role for CDK6 in leukemic progenitor cells

PROVIDER: PRJNA646386 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12225127.fastq.gz	Fastqsanger.gz
	SRR12225128.fastq.gz	Fastqsanger.gz
	SRR12225129.fastq.gz	Fastqsanger.gz
	SRR12225130.fastq.gz	Fastqsanger.gz
	SRR12225131.fastq.gz	Fastqsanger.gz

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A cutting-edge approach unravels a novel role for CDK6 in leukemic progenitor cells

Project description:CDK6 induces a complex transcriptional program to block p53 in hematopoietic cells. CDK6 binds to the promoters of genes including p53-antagonists. Cells lacking CDK6 kinase function are required to mutate p53 to achieve a fully transformed immortalized state.

2021-01-22 | GSE154464 | GEO

CDK6 as key regulator of hematopoietic and leukemic stem cell activation.

Project description:The cyclin-dependent kinases (CDK) CDK6 and CDK4 have redundant functions in regulating cell-cycle progression. We describe a novel role for CDK6 in hematopoietic and leukemic stem cells (HSCs and LSCs) that exceeds its function as cell-cycle regulator. Although hematopoiesis appears regular under steady state conditions Cdk6-/- HSCs do not efficiently repopulate upon competitive transplantation and Cdk6-deficient mice are significantly more susceptible to 5-fluorouracil (5-FU) treatment. We find that activation of HSCs requires CDK6, which interferes with transcription of key regulators including Egr1. The central role of Egr1 is supported by transcriptional profiling of HSCs. The impaired repopulation capacity extends to BCR-ABLp210+ leukemic stem cells. Transplantation with BCR-ABLp210+-infected bone marrow (BM) from Cdk6-/- mice fails to induce disease although recipient mice do harbor LSCs. Egr1 knock-down in cdk6-/- BCR-ABLp210+ LSKs significantly enhances colony formation underlining the importance of the Cdk6-Egr1 axis. Our findings define CDK6 as an important regulator of stem cell activation and as essential component of a transcriptional complex that suppresses Egr1 in HSCs and LSCs. Four-condition experiment, Untreated or polyI:C-treated CDK6-/- cells versus untreated or polyI:C-treated wild-type cells. Biological replicates: 3 untreated replicates, 3 polyI:C-treated replicates.

2015-02-20 | E-GEOD-62012 | biostudies-arrayexpress

CDK6 as key regulator of hematopoietic and leukemic stem cell activation.

2015-02-20 | GSE62012 | GEO

Nanopore Sequencing as a Cutting-Edge Technology for Medulloblastoma Classification

Project description:Nanopore Sequencing as a Cutting-Edge Technology for Medulloblastoma Classification

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RNA-seq data from VavCre;Jak2+/+; Cdk6+/+, VavCre;Jak2V617F; Cdk6+/+, VavCre;Jak2V617F; Cdk6-/-, VavCre; Jak2+/+; Cdk6-/- murine bone marrow LSK cells and VavCre; Jak2V617F; Cdk6+/+ Palbociclib treated murine bone marrow LSK cells

Project description:We describe a critical role for Cdk6 in JAK2V617F+ MPN evolution. The absence of Cdk6 ameliorates clinical symptoms and prolongs survival of JAK2V617F fl/+ vav-Cre mice. The Cdk6 protein interferes with three hallmarks of disease: besides regulating malignant stem cell quiescence, it promotes NFkB signaling and contributes to cytokine production while inhibiting apoptosis. The treatment with palbociclib did not mirror these effects, showing that the functions of Cdk6 in MPN pathogenesis are largely kinase-independent.

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ChIP sequencing experiment of HA-tagged WT CDK6 or of a C-terminally truncated variant of CDK6 (CDK6 delta-C) in BCR-ABL1 expressing cell lines

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2024-06-30 | E-MTAB-13798 | biostudies-arrayexpress

Gene expression profiling of murine BCR-ABL+ CDK6-wt and CDK6-KO cells

Project description:Dertermination of chromatin accessibility in murine BCR-ABL+ CDK6-wt and CDK6-KO cells

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Interactome of C-terminally truncated CDK6

Project description:Pre/pro-B-cell lines were generated from bone marrow cells of Cdk6-/- mice by retroviral overexpression of the BCR-ABL (p185) fusion oncogene. These cell lines were transduced with constructs expressing HA-tagged versions of wildtype Cdk6 or of a C-terminally truncated variant of Cdk6 (HA-Cdk6-ΔC). To study the interactome of HA-Cdk6-ΔC immunoprecipitation followed by mass spectrometry was performed.

2024-12-19 | PXD058474 | Pride

CDK6 antagonizes p53-induced responses during tumorigenesis

2018-08-06 | GSE113752 | GEO