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A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia [RNA-Seq]

ABSTRACT: A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia [RNA-Seq]

PROVIDER: PRJNA742549 | ENA |

REPOSITORIES: ENA

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A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia [ChIP-Seq]

Project description:Acute myeloid leukemias (AMLs) with the NUP98-NSD1 or MLL gene rearrangement (MLL-r) share transcriptomic profiles featured with stemness-related gene signatures and display poor prognosis in the clinic. However, the molecular underpinnings of AML aggressiveness and stemness remain far from clear. Here, we report that the enzymatic activity of Polycomb Repressive Complex 2 (PRC2) is crucial for maintenance of tumorigenicity in NUP98-NSD1+ AML, consistent to its role in MLL-r AML. Transcriptomic analysis revealed Kdm5b, a lysine demethylase gene carrying the “bivalent domain” chromatin feature in AML, to be directly repressed by PRC2. While ectopic expression of Kdm5b suppressed AML growth, its depletion in AML not only promoted tumorigenicity but also significantly attenuated anti-AML effects by PRC2 inhibitors, thus demonstrating an involvement of the PRC2-|Kdm5b axis for AML oncogenesis. Lower KDM5B expression is positively correlated with poorer prognosis of human AML patients. RNA-seq, ChIP-seq and CUT&RUN based genomic profilings also showed that Kdm5b directly binds to and represses AML stemness genes. In contrast to an essential involvement for its various chromatin-associating domains, Kdm5b’s demethylase function was found to be dispensable for AML suppression, indicating a scaffold role in assembling gene-repressive complexes. Collectively, this study describes a molecular axis involving histone modifiers (PRC2 and Kdm5b) for sustaining the malignant features of AML, implicative of potential therapeutics.

2022-02-22 | GSE179824 | GEO

A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia [CUT&RUN]

2022-02-22 | GSE179168 | GEO

A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia [RNA-Seq]

2022-02-22 | GSE179167 | GEO

A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia

Project description:A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia

| PRJNA745183 | ENA

A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia [ChIP-Seq]

Project description:A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia [ChIP-Seq]

| PRJNA745187 | ENA

A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia [CUT&RUN]

Project description:A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia [CUT&RUN]

| PRJNA742550 | ENA

A PRC2-KDM5B-stemness regulatory axis sustains tumorigenicity of acute myeloid leukemia

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-02-22 | GSE179826 | GEO

PRC1 Sustains the Memory of Neuronal Fate Independent of PRC2 Function

Project description:PRC1 Sustains the Memory of Neuronal Fate Independent of PRC2 Function

| PRJNA732648 | ENA

High-fat diet activated fatty acid oxidation mediates intestinal stemness and tumorigenicity

Project description:High-fat diet activated fatty acid oxidation mediates intestinal stemness and tumorigenicity

| PRJNA692179 | ENA

CRISPR/Cas9 screens reveal that hexokinase 2 enhances cancer stemness and tumorigenicity

Project description:CRISPR/Cas9 screens reveal that hexokinase 2 enhances cancer stemness and tumorigenicity

| PRJNA766529 | ENA

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