FIP1L1 knockdown in Kasumi-1 AML cells
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ABSTRACT:
PROVIDER: PRJNA610629 | ENA |
REPOSITORIES: ENA
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Project description:Post-transcriptional regulation has emerged as a driver for leukemia development and an avenue for therapeutic targeting. Among post-transcriptional processes, alternative polyadenylation (APA) is globally dysregulated across cancer types. However, limited studies have focused on the prevalence and role of APA in leukemia. Furthermore, it is poorly understood how altered poly(A) site usage of individual genes contributes to malignancy or whether targeting global APA patterns might alter oncogenic potential. By performing 3’RNA sequencing on acute myeloid leukemia (AML) patient samples and healthy hematopoietic stem and progenitor cells (HSPCs), we show that patient cells exhibit global 3’ untranslated region (UTR) shortening and coding sequence (CDS) lengthening due to differences in poly(A) site usage. Among APA regulators, FIP1L1 expression correlated with the degree of APA dysregulation and knockdown of this RNA-binding protein (RBP) reversed the global trends seen in patients. Importantly, FIP1L1 knockdown induced differentiation of t(8;21) cells by promoting 3’UTR lengthening and downregulation of fusion oncoprotein AML1-ETO. In non-t(8;21) cells, knockdown also promoted differentiation by attenuating mTORC1 signaling and reducing MYC protein levels. Our study gives mechanistic insight into the role of APA in AML pathogenesis and provides evidence that targeting global APA patterns can overcome the differentiation block of AML patients.
2021-12-31 | GSE146475 | GEO
Project description:Purpose: To clarify the function of TIM-3 signaling in AML cells. Analysis of lentiviral shRNA-mediated knockdown of TIM-3 in TIM-3+ acute myeloid leukemia (AML) cell line, KASUMI-3. Consistent with our previous study (Kikushige et al., Cell Stem Cell 2015) revealing the presence of TIM-3/galectin-9 autocrine loop and its constitutive signaling in AML, KD of receptor,TIM-3, alone significantly impaired the proliferation of KASUMI-3 in vitro and in vivo.
2019-04-26 | GSE130328 | GEO
Project description:Kasumi-1 AML cells that were transfected in triplicate with AML1-ETO or luciferase siRNA constructs by either Amaxa nucleofection or Biorad siLentFect and incubated for 96 hours. Microarrays used to discover an AML1-ETO signature for a GE-HTS screen to identify AML1-ETO modulators. Experiment Overall Design: Kasumi-1 AML cells incubated for 96 hours after they were transfected in triplicate with AML1-ETO or luciferase siRNA constructs by either Amaxa nucleofection or Biorad siLentFect along with three control samples not transfected with a construct.
2009-05-11 | E-GEOD-15646 | biostudies-arrayexpress
Project description:Kasumi-1 AML cells that were transfected in triplicate with AML1-ETO or luciferase siRNA constructs by either Amaxa nucleofection or Biorad siLentFect and incubated for 96 hours. Microarrays used to discover an AML1-ETO signature for a GE-HTS screen to identify AML1-ETO modulators.
2009-05-01 | GSE15646 | GEO
Project description:Nearly 10-15% of all acute myeloid leukemia (AML) cases are caused by a recurring chromosomal translocation between 8 and 21, t(8;21). The t(8;21) translocation generates the AML1-ETO leukemia fusion protein. AML1-ETO promotes leukemogenesis by transcriptionally dysregulating important cell-fate genes. Here, to better understand how AML1-ETO deregulates transcription, we performed paired ChIP-Seq analyses of sequence-specific transcription factors, coactivators, corepressors, HDACs, RNA Pol II and acetyl-histone marks in both control and AML1-ETO-depleted Kasumi-1 t(8;21) AML cells.
2020-02-14 | GSE131939 | GEO
Project description:GATA-2 is a master regulator of hematopoiesis which controls expression of multiple genes and is implicated in acute myeloid leukemia (AML). However, the molecular mechanism how GATA-2 deregulation causes leukemogenesis is still unclear. In this study, GATA-2 ChIP-squ analysis was conducted in Kasumi-3 AML cell line to identify GATA-2 target genes which play important roles in the pathogenesis of AML. ChIP with GATA-2 antibody was conducted in Kasumi-3 AML cell line and ChIP-seq profile was generated by deep sequencing.
2016-08-05 | E-GEOD-84782 | biostudies-arrayexpress
Project description:The AML1-ETO fusion protein, a transcription factor generated by the t(8;21) translocation in acute myeloid leukaemia (AML), dictates a leukemic program by increasing self-renewal and inhibiting differentiation. Here we demonstrate that the histone demethylase JMJD1C functions as a co-activator for AML1-ETO and is required for its transcriptional program. JMJD1C is directly recruited by AML1-ETO to its target genes and regulates their expression by maintaining low H3K9me2 levels. Analyses in JMJD1C knockout mice also establish a JMJD1C requirement for AML1-ETOâs ability to increase proliferation. We also show a critical role for JMJD1C in the survival of multiple human AML cell lines, suggesting that it is required for leukemic programs in different AML cell types through its association with key transcription factors. Examination of JMJD1C and LYL1 chromatin binding in Kasumi-1 cells, HL-60 cells, NB-4 cells and THP-1 cells, including ChIP-seqs of JMJD1C and LYL1, and input DNAs for Kasumi-1, HL-60, NB4.
2015-11-02 | E-GEOD-63484 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series:; GSE15646: Kasumi-1 AML1-ETO knockdown samples; GSE15647: U937 AML1-ETO inducible samples Experiment Overall Design: Refer to individual Series
2009-05-08 | E-GEOD-15648 | biostudies-arrayexpress
Project description:RASSF2 knockdown in THP-1 AML cells
| PRJNA592002 | ENA
Project description:Paired ChIP-Seq studies of Kasumi-1 t(8;21) AML cells
| PRJNA545353 | ENA