GEO series

Aberrantly Expressed Mitochondrial Lipid Kinase, AGK Activates JAK2-Histone H3 Axis and BCR Signal: A Mechanistic Study with Implication in CLL Therapy

GSE277432 Homo sapiens (human) RNA-seq (gene expression) 10 samples Submitted 2024/11/20 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 10 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: Chronic lymphocytic leukemiaThis series is part of our curated briefing on it.
Samples: 10 samples: 5 × PGroups 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: Aberrantly Expressed Mitochondrial Lipid Kinase, AGK, Activates JAK2-Histone H3 Axis and BCR Signal: A Mechanistic Study with Implication in CLL TherapyClinical cancer research : an official journal of the American Association for Cancer Research · 2025

Summary (written by the submitters)

Purpose: Although the B-cell receptor (BCR) signal plays a critical role in CLL cell survival and a target of current therapies (ibrutinib targets Bruton’s tyrosine kinase; idelalisib targets PI3Kδ), contribution of the cytokine-driven JAK2 pathway to the “CLL cell-survival signaling network” is largely undefined. Experimental Design: CLL patients were enrolled to investigate expression/activation of JAK2 and acylglycerol kinase (AGK), and their functional implication in primary CLL cell survival.

Read the full summary ↓

A series of biochemical and molecular biology assays were employed to uncover the underlying mechanism. Results: We detected that compared to normal B-cells, CLL cells aberrantly express constitutively active JAK2. Mechanistically, HSP90 forms a chaperoning complex with JAK2, resulting in its aberrant accumulation in CLL cells. We also discovered aberrant upregulation of a novel mitochondrial lipid kinase, AGK, which remains complexed with HSP90 in CLL cells activating JAK2. Although AGK is typically mitochondrial, we detected its nuclear localization in association with JAK2 in some CLL cells. Functionally, JAK2 phosphorylates its non-canonical substrate, histone H3(Y41), but not STAT3, activating transcription of diverse sets of genes in a patient-specific manner. Additionally, JAK2 activates the BCR-signal in CLL cells via LYN/BTK axis. Targeted inhibition of JAK2 as monotherapy, or in combination with the BCR-inhibitors or venetoclax (a BCL2-inhibitor) induced apoptosis synergistically in CLL cells. Conclusions: These findings suggest that aberrantly expressed AGK activates JAK2, independent of cytokine, leading to activation of diverse sets of gene transcription in CLL cells. Combined targeting of JAK2 and BCR signals or BCL2 may be effective in some CLL patients.

Published in

Aberrantly Expressed Mitochondrial Lipid Kinase, AGK, Activates JAK2-Histone H3 Axis and BCR Signal: A Mechanistic Study with Implication in CLL Therapy

Mamidi MK, Sinha S, Mendez MT et al. · Clinical cancer research : an official journal of the American Association for Cancer Research 2025 · PMID 39636206 · doi:10.1158/1078-0432.CCR-24-1192

This dataset

Open GSE277432 in finder → Find more human RNA-seq datasets → Chronic lymphocytic 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 GSE277432_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 PRJNA1162160 and SRA study SRP533249. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39636206) ↗

Study design

5 × P

Supports a between-group comparison across 5 samples.

How we read this: 1 replicated groups read from 10 sample titles; they account for 5 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

GSM8522391 P23_JAK
GSM8522392 P23 P
GSM8522393 P53_JAK
GSM8522394 P53 P
GSM8522395 P63_JAK
GSM8522396 P63 P
GSM8522397 P22_JAK
GSM8522398 P22 P
GSM8522399 P21_JAK
GSM8522400 P21 P

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.