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Effect of depletion of KDM4C on gene expression of JAK2-mutated HEL erythroleukemia cells [RNA-seq]

ABSTRACT: Effect of depletion of KDM4C on gene expression of JAK2-mutated HEL erythroleukemia cells [RNA-seq]

PROVIDER: PRJNA838374 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19215800_1.fastq.gz	Fastqsanger.gz
	SRR19215800_2.fastq.gz	Fastqsanger.gz
	SRR19215804_1.fastq.gz	Fastqsanger.gz
	SRR19215804_2.fastq.gz	Fastqsanger.gz
	SRR19215793_1.fastq.gz	Fastqsanger.gz

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Effect of genom-wide depletion on gene expression during treatment with the JAK2 inhibitor Ruxolitinib of JAK2 mutated HEL erythroleukemia cells [CRISPR]

Project description:In order to confirm the functional dependency on KDM4C under treatment conditions with the JAK-inhibitor ruxolitinib (RUX), we applied a genome-wide CRISPR-Cas9 screen in the human JAK2-mutated cell line HEL by CRISPR/Cas9.

2022-05-18 | GSE203059 | GEO

Effect of depletion of KDM4C on gene expression of JAK2-mutated HEL erythroleukemia cells [RNA-seq]

Project description:To investigate the function of KDM4C in progression of leukemia, we established HEL-Cas9 cell lines in which the target gene has been knocked out by CRISPR/Cas9. We then performed transcriptome analysis using data obtained from RNA-seq of control or KDM4C depletd cells.

2022-05-18 | GSE203060 | GEO

Effect of genom-wide depletion on gene expression during treatment with the JAK2 inhibitor Ruxolitinib of JAK2 mutated HEL erythroleukemia cells [CRISPR]

Project description:Effect of genom-wide depletion on gene expression during treatment with the JAK2 inhibitor Ruxolitinib of JAK2 mutated HEL erythroleukemia cells [CRISPR]

| PRJNA838373 | ENA

Expression data of HEL cells with or without LY2784544 and GRN163L

Project description:The mutant JAK2v617F is a driver of myeloproliferative neoplasms(MPNs). Consequently, several JAK2 inhibitors are currently being studied in clinical trials. The most investigated JAK2 inhibitor, Ruxolitinib, provides significant and sustained improvements in spleen related and constitutional symptoms secondary to the disease and represents a milestone in the treatment of myelofibrosis. However, JAK2 inhibitors are non-curative and murine experiments have shown that JAK2 inhibitors don?t eradicate MPN stem cells. In the present study, we determined the effect of the specific JAK2V617F inhibitor LY2784544 on leukemic stem (CD34+) cells (LSCs) using the JAK2V617F-bearing erythroleukemia cell line HEL. The LY2784544 treatment caused a transient proliferation inhibition and apoptosis of HEL cells, but a recovery occurred within a week. Thereafter, the continuous exposure of HEL cells to LY2784544 induced the accumulation of CD34+ LSCs, and the CD34+ cell fraction increased from 8% to over 90% by week 9, which was accompanied by substantially increased clonogenic potentials. A whole-transcript expression analysis revealed a significantly enhanced expression of the stem cell factor KLF4 in LY2784544 treated HEL cells. Inhibiting KLF4 expression attenuated LY2784544-mediated accumulation of CD34+ LSCs. Moreover, we further identified that the telomerase inhibitor GRN163L abolished the LY2784544-mediated CD34+ cell enrichment. Our findings collectively suggest that JAK2 inhibitors may cause enrichment of LSCs and are therefore unlikely to cure MPN as a monotherapy. Moreover, simultaneously targeting JAk2V617F and KLF4 or telomerase may be a novel strategy for MPN treatment.

2019-12-07 | GSE141602 | GEO

Splicing factor Ybx1 maintains persistent Jak2-mutated neoplasms via Mknk1-ERK-signaling

Project description:Janus kinases (Jak) mediate cytokine, hormone and growth factor responses in hematopoietic cells. Jak2 is one of the most frequently mutated genes in the aging hematopoietic system and in hematopoietic cancers. Mutations in Jak constitutively activate downstream signaling and are drivers of myeloproliferative neoplasms (MPN). In clinical use, Jak-inhibitors have incomplete effects on overall disease burden of Jak2 mutated clones, prompting us to investigate the mechanism underlying disease persistence. By in-depth phospho-proteome profiling we here identify proteins involved in mRNA processing as targets of mutant Jak2. Inactivation of the post-translationally modified Jak2-target Ybx1 sensitizes Jak-inhibitor persistent cells to apoptosis and results in RNA mis-splicing, retained intron enrichment and disruption of the transcriptional control of extracellular signal-regulated kinase (ERK) signaling. In combination with pharmacological Jak-inhibition it induces apoptosis in Jak2-dependent murine and primary human cells, leading to in vivo regression of the malignant clones and inducing remission. This identifies and validates a novel cell-intrinsic mechanism how differential protein phosphorylation results in splicing-dependent alterations of Jak2-ERK-signaling and the maintenance of Jak2V617F malignant clones. Therapeutic targeting of Ybx1 dependent ERK-signaling in combination with Jak2-inhibition may eradicate Jak2-mutated cells.

2020-08-20 | PXD006921 | Pride

Splicing factor Ybx1 mediates persistence of Jak2-mutated neoplasms

Project description:Janus kinases (Jak) mediate cytokine, hormone and growth factor responses in hematopoietic cells. Jak2 is one of the most frequently mutated genes in the aging hematopoietic system and in hematopoietic cancers. Mutations in Jak constitutively activate downstream signaling and are drivers of myeloproliferative neoplasms (MPN). In clinical use, Jak-inhibitors have incomplete effects on overall disease burden of Jak2 mutated clones prompting us to investigate the mechanism underlying disease persistence. By in-depth phospho-proteome profiling we here identify proteins involved in mRNA processing as targets of mutant Jak2. Inactivation of the post-translationally modified Jak2-target Ybx1 sensitizes Jak-inhibitor persistent cells to apoptosis and results in RNA mis-splicing, retained intron enrichment and disruption of the transcriptional control of extracellular signal-regulated kinase (ERK) signaling. In combination with pharmacological Jak-inhibition it induces apoptosis in Jak2-dependent murine and primary human cells, leading to in vivo regression of the malignant clones and inducing remission. This identifies and validates a novel cell-intrinsic mechanism how differential protein phosphorylation results in splicing-dependent alterations of Jak2-ERK-signaling and the maintenance of Jak2V617F malignant clones. Therapeutic targeting of Ybx1 dependent ERK-signaling in combination with Jak2-inhibition may eradicate Jak2-mutated cells.

2018-12-07 | GSE123417 | GEO

RNA splicing factor Ybx1 maintains persistent Jak2-mutated neoplasms via Mknk1-ERK-signaling

Project description:Measurement of DNA-binding of YBX1 in the HEL cell line (JAK2V617F mutated human cells)

2020-03-11 | GSE146717 | GEO

Genome-wide occupancy of LSD1 in HEL human erythroleukemia cell line.

Project description:Genome-wide occupancy of LSD1 in HEL human erythroleukemia cell line.

| PRJNA607086 | ENA

Splicing factor Ybx1 maintains persistent Jak2-mutated neoplasms via Mknk1-ERK-signaling persistent clones in Jak2-mutated neoplasms

Project description:Splicing factor Ybx1 maintains persistent Jak2-mutated neoplasms via Mknk1-ERK-signaling persistent clones in Jak2-mutated neoplasms

| PRJNA644892 | ENA

PolyA RNA sequencing of HEL human erythroleukemia cell line under LSD1 inhibition

Project description:PolyA RNA sequencing of HEL human erythroleukemia cell line under LSD1 inhibition

| PRJNA607075 | ENA