Unknown

Dataset Information

0

The AAA+ATPase RUVBL2 is essential for the oncogenic function of c-MYB in acute myeloid leukemia.


ABSTRACT: Subtype-specific leukemia oncogenes drive aberrant gene expression profiles that converge on common essential mediators to ensure leukemia self-renewal and inhibition of differentiation. The transcription factor c-MYB functions as one such mediator in a diverse range of leukemias. Here we show for the first time that transcriptional repression of myeloid differentiation associated c-MYB target genes in AML is enforced by the AAA+ ATPase RUVBL2. Silencing RUVBL2 expression resulted in increased binding of c-MYB to these loci and their transcriptional activation. RUVBL2 inhibition resulted in AML cell apoptosis and severely impaired disease progression of established AML in engrafted mice. In contrast, such inhibition had little impact on normal hematopoietic progenitor differentiation. These data demonstrate that RUVBL2 is essential for the oncogenic function of c-MYB in AML by governing inhibition of myeloid differentiation. They also indicate that targeting the control of c-MYB function by RUVBL2 is a promising approach to developing future anti-AML therapies.

SUBMITTER: Armenteros-Monterroso E 

PROVIDER: S-EPMC6887538 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

The AAA+ATPase RUVBL2 is essential for the oncogenic function of c-MYB in acute myeloid leukemia.

Armenteros-Monterroso Elena E   Zhao Lu L   Gasparoli Luca L   Brooks Tony T   Pearce Kerra K   Mansour Marc R MR   Martens Joost H A JHA   de Boer Jasper J   Williams Owen O  

Leukemia 20190528 12


Subtype-specific leukemia oncogenes drive aberrant gene expression profiles that converge on common essential mediators to ensure leukemia self-renewal and inhibition of differentiation. The transcription factor c-MYB functions as one such mediator in a diverse range of leukemias. Here we show for the first time that transcriptional repression of myeloid differentiation associated c-MYB target genes in AML is enforced by the AAA+ ATPase RUVBL2. Silencing RUVBL2 expression resulted in increased b  ...[more]

Similar Datasets

2020-04-14 | GSE117224 | GEO
| PRJNA481496 | ENA
| S-EPMC5976475 | biostudies-literature
| S-EPMC5550326 | biostudies-other
| S-EPMC5760651 | biostudies-literature
| S-EPMC3981677 | biostudies-literature
| S-EPMC7658230 | biostudies-literature
| S-EPMC5764110 | biostudies-literature
2021-02-24 | GSE163470 | GEO
| S-EPMC4406710 | biostudies-literature