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Targeting a Lineage-Specific PI3Kɣ/AKT Signaling Module in Acute Myeloid Leukemia Using a Heterobifunctional Degrader Molecule

GSE260759 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2024/04/30 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 24 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
24 samples: 6 conditions, mostly with about 4 replicates eachGroups 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.
Paper
Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader moleculeNature cancer · 2024
Summary (written by the submitters)
Dose-limiting toxicity poses a major limitation to the clinical utility of targeted cancer therapies, often arising from target engagement in non-malignant tissues. This obstacle can be minimized by targeting cancer dependencies driven by proteins with tissue- and/or tumor-restricted expression. Here, we show that in acute myeloid leukemia (AML), suppression of the myeloid-restricted PIK3CG/p110 -PIK3R5/p101 axis blocks AKT signaling, compromises cell fitness, and sensitizes to established AML therapies.
Read the full summary ↓
Importantly, we find that existing small molecule inhibitors against PIK3CG are insufficient to achieve a sustained long-term anti-leukemic effect. To address this concern, we developed a PROteolysis-TArgeting Chimera (PROTAC) heterobifunctional molecule that specifically degrades PIK3CG and potently suppresses AML progression alone and in combination with venetoclax in human AML cell lines, primary AML patient samples, and syngeneic mouse models.
Published in
Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule
Kelly LM, Rutter JC, Lin KH et al. · Nature cancer 2024 · PMID 38816660 · doi:10.1038/s43018-024-00782-5
This dataset
Open GSE260759 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 GSE260759_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 PRJNA1083256 and SRA study SRP493066. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38816660) ↗
Study design
6 conditions, mostly with about 4 replicates each
MOLM14_DMSO ×4 MOLM14_AZ2 ×4 MOLM14_ARM ×4 OCIAML2_DMSO ×4 OCIAML2_AZ2 ×4 OCIAML2_ARM ×4

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 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

Search all human RNA-seq datasets in GEO →

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