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Targeting Y593-phosphorylated DDX5 triggers mitochondrial dysfunction and synergizes with BCL2 inhibition in acute myeloid leukemia

GSE324645 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/05/01 Platform GPL28038
At a glance

RNA-seq (gene expression) · human · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Acute myeloid leukemiaThis series is part of our curated briefing on it.
Samples
12 samples: 3 × MOLM-14 cells, shControl, 96 hours, biological replicate # vs 3 × MOLM-14 cells, shDDX5, 96 hours, biological replicate # vs 3 × MOLM-14 cells, DMSO, 6 hours, biological replicate # vs 3 × MOLM-14 cells, RX-5902, 6 hours, biological replicate #Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Acute myeloid leukemia (AML) remains a lethal malignancy with limited therapeutic durability. DEAD-box RNA helicase 5 (DDX5) is highly expressed in AML and associated with poor outcome, yet its mechanistic role and therapeutic tractability are incompletely defined. Here, we identify phosphorylation at tyrosine 593 (Y593) of DDX5 as a therapeutic vulnerability in AML.
Read the full summary ↓
We show that DDX5 is constitutively phosphorylated at Y593 in AML cells independent of Src or c-Abl activity. While genetic depletion of DDX5 suppresses AML growth, phosphorylation-deficient Y593F knock-in mutants show that Y593 phosphorylation is dispensable for baseline proliferation but is required to maintain mitochondrial integrity and define the BCL-2 family–controlled apoptotic threshold. Targeting Y593-phosphorylated DDX5 with the small-molecule RX-5902 destabilizes β-catenin and, more importantly, triggers acute mitochondrial dysfunction characterized by impaired oxidative phosphorylation, permeabilizes mitochondrial outer membranes, and increases BCL-2 dependence. Accordingly, inhibition of Y593-phosphorylated DDX5 represents a mitochondrial sensitizer that creates vulnerability to BCL-2 blockade. Consistent with this mechanism, RX-5902 strongly synergizes with venetoclax across AML cell lines, primary patient samples, and xenograft models. Together, these findings establish Y593-phosphorylated DDX5 as an actionable regulator of mitochondrial apoptotic priming in AML and support combined targeting of DDX5 and BCL-2 as a rational therapeutic strategy.
This dataset
Open GSE324645 in finder → Find more human RNA-seq datasets → Acute myeloid leukemia landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE324645_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1436483 and SRA study SRP683145. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × MOLM-14 cells, shControl, 96 hours, biological replicate # vs 3 × MOLM-14 cells, shDDX5, 96 hours, biological replicate # vs 3 × MOLM-14 cells, DMSO, 6 hours, biological replicate # vs 3 × MOLM-14 cells, RX-5902, 6 hours, biological replicate #

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
More Acute myeloid leukemia datasets

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