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Proteogenomic subtyping of acute myeloid leukemia and ex-vivo drug response profiling for precision therapies.

ABSTRACT: We have performed a comprehensive proteomic analysis of clinical patient samples of acute myeloid leukemia (AML) alongside genome-, transcriptome- and ex-vivo drug response profiling.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, Myeloid Cell, Blood, Bone Marrow Cell

DISEASE(S): Acute Leukemia

SUBMITTER: Rozbeh Jafari

LAB HEAD: Prof Janne

PROVIDER: PXD061758 | Pride | 2026-03-23

REPOSITORIES: Pride

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			Action	DRS
	AML_SSF_PRO_set1_IPG3-10_fr01.raw	Raw
	AML_SSF_PRO_set1_IPG3-10_fr02.raw	Raw
	AML_SSF_PRO_set1_IPG3-10_fr03.raw	Raw
	AML_SSF_PRO_set1_IPG3-10_fr04.raw	Raw
	AML_SSF_PRO_set1_IPG3-10_fr05.raw	Raw

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1 - 5 of 2211

Publications

Midostaurin response in AML is shaped by a progenitor-like cell state selectively targeted by SMAC mimetics.

Struyf Nona N Gezelius Henrik H Lundmark Anders A Barizza Chiara C Ploeger Hidde H Rico Pizarro Lucia L Vesterlund Mattias M Mermelekas Georgios G Österroos Albin A Bohlin Anna A Bengtzén Sofia S Hamberg Levedahl Kerstin K Jafari Rozbeh R Orre Lukas M LM Lehtiö Janne J Östling Päivi P Seashore-Ludlow Brinton B Nordlund Jessica J Lehmann Sören S Kallioniemi Olli O Erkers Tom T

NPJ precision oncology 20260311 1

FLT3-mutated acute myeloid leukemia (AML) remains difficult to treat due to frequent resistance to FLT3 inhibitors like midostaurin. In this study, we observed a progenitor-like CD38<sup>+</sup>CD45RA<sup>+</sup> leukemic cell population that may be associated with midostaurin resistance. Midostaurin-resistant cells display disrupted membrane architecture and a shift in signaling from STAT5 to PI3K/AKT, favoring survival over apoptosis. Functional drug testing was consistent with clinical respon ...[more]

PMID: 41813823

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Proteogenomic subtyping of chronic lymphocytic leukemia identifies subgroups with contrasting clinical outcome and distinct ex-vivo drug response profile

Project description:We have performed a comprehensive proteomic analysis of clinical patient samples of chronic lymphocytic leukemia (CLL) alongside genome-, transcriptome- and ex-vivo drug response profiling. Trisomy 12 and IGHV mutation status had the strongest impact on the proteome and transcriptome; and SF3B1 mutations preferentially affected the proteome. Unsupervised clustering of the proteome data partitioned CLL patients into six protein based subgroups (PG) with contrasting clinical behavior. PG1-4 could be explained by the impact of trisomy 12 and IGHV mutation status on protein abundances and another subgroup (PG6), was enriched for TP53 mutations. In addition we uncovered a new subgroup (PG5) only detectable from the proteome, characterized by low expression of central B-cell receptor proteins, altered splicing, metabolic reprogramming and increased sensitivity to proteasomal inhibition. https://www.ebi.ac.uk/pride/archive/projects/PXD024544

2022-10-17 | PXD028936 | Pride

Proteogenomic subtyping of chronic lymphocytic leukemia identifies subgroups with contrasting clinical outcome and distinct ex-vivo drug response profile

2024-06-21 | PXD017453 | Pride

Transcriptional profiling of Th1, Th2, Th9, and Th17 T cell clones

Project description:We next sought to identify the transcriptional program that differentiates IL-9+Th2 cells from “conventional” Th2 cells. To this end, we selected representative Th1, Th17, Th2, and IL-9+Th2 clones (Figure 5A) and determined their transcriptome in the resting state and at different time points after activation using RNAseq. Peripheral Blood Mononuclear Cells (PBMC) were isolated by Ficoll-Plaque Plus (GE Healthcare, UK) density gradient centrifugation. Human CD4+ T cells were isolated from PBMC by EasySep positive selection kit (Stemcell Technologies) according to manufacturer’s instruction. Positively selected CD4+ T cells were washed with PBS and stained for subsequent Th cell subset sorting. Memory Th cell subsets were sorted to over 90% purity according to their expression of chemokine receptors from CD45RA-CD25-CD8-CD3+ cells: Th1(CXCR3+CCR8-CCR6-CCR4-), Th2 (CXCR3-CCR8-CCR6-CCR4+), Th17 (CXCR3-CCR8-CCR6+CCR4+), Th9 (CXCR3-CCR8+CCR6-CCR4+). Single cell Th subset clones were directly sorted into 96well plate according to their expression of chemokine receptors (see above). Single cell clones were expanded and maintained by periodic restimulation with PHA (phytohaemaglutinine, 1 µg/ml, Sigma-Chemicals) and irradiated allogenic feeder cells (5x104/well) in culture medium. T cells were polyclonally activated using beads coated with antibodies against CD3, CD2, and CD28 (T cell/bead = 2:1, human T cell activation/expansion Kit, Miltenyi). Cell cultures were sampled before activation (time 0h) and 2, 4, 6, 9, 12, 24, and 48 hours after activation.

2017-11-10 | E-MTAB-5739 | biostudies-arrayexpress

Transcriptional profiling of human IL-9R+ T helper cells in presence of recombinant IL-9 against untreated control

Project description:To study the effect of paracrine interleukin-9 (IL-9) on T helper cells, we incubated IL-9R+ T helper cells isolated from blood (5 samples) and skin (3 samples) with or without IL-9 for 12h and the transcriptome was analyzed by bulk RNA-seq.

2022-10-31 | E-MTAB-12204 | biostudies-arrayexpress

Transcriptional profiling of human in vitro primed Th1, Th2, Th9 and Treg T cells

Project description:To test whether human in vitro primed Th9 cells recapitulate the core pathogenic Th2 cell phenotype, we differentiated naïve T cells into Th1 (IL-12), Th2 (IL-4), Th9 (IL-4+TGF-β), and iTreg (TGF-β). After 7 days transcriptomic profiling by bulk RNA-seq was performed.

2022-10-31 | E-MTAB-12199 | biostudies-arrayexpress

Transcriptional profiling of human Th9 T cell clones treated with GW9662 against untreated control

Project description:To investigate the role of PPAR-γ in human TH cells, transcriptional response of activated “TH9” clones to treatment with GW9662, a potent PPAR-γ antagonist was assessed. “TH9” cell clones were incubated with GW9662 for 48h and activated with αCD3/2/28 for 12 h. Transcriptomic profiling was performed by bulk RNA-seq. To generate TH9 clones, Peripheral Blood Mononuclear Cells (PBMC) were isolated by Ficoll-Plaque Plus (GE Healthcare, UK) density gradient centrifugation. Human CD4+ T cells were isolated from PBMC by EasySep positive selection kit (Stemcell Technologies) according to manufacturer’s instruction. Positively selected CD4+ T cells were washed with PBS and stained for subsequent TH cell subset sorting. Effector memory “TH9” cells (CXCR3-CCR8+CCR6-CCR4+) were sorted to over 90% purity according to their expression of chemokine receptors from CD45RA-CD25-CD8-CD3+ cells. Single cell “TH9” clones were directly sorted into 96well plate according to their expression of chemokine receptors (see above). Single cell clones were expanded and maintained by periodic restimulation with PHA (1 µg/ml, Sigma-Chemicals) and irradiated allogenic feeder cells (5x104/well) in culture medium.

2022-10-31 | E-MTAB-12197 | biostudies-arrayexpress

Transcriptional profiling of human in vitro primed Th9 T cells (day 20) treated with GW9662 against untreated control

Project description:To investigate the role of PPAR-γ in human TH cells, transcriptional response in vitro primed Th9 cells to treatment with GW9662, a potent PPAR-γ antagonist was assessed. In vitro primed Th9 cells (day 20) were incubated with GW9662 for 48h. Transcriptomic profiling was performed by bulk RNA-seq. To generate in vitro primed Th9 cells, human naive T cells were isolated from PBMCs using the EasySep™ Human naive CD4+ T Cell Isolation Kit (Stemcell Technologies) as per the manufacturer’s instructions. Naive T cells were stimulated with αCD3/CD2/CD28 beads (T cell/bead = 2:1, Miltenyi) and primed into effector CD4+ Th9 cells with IL-4 (50 ng/ml) and TGF-β (5 ng/ml) (R&D Systems). From cell culture initiation to analysis, the culture medium was supplemented with the indicated cytokines every other day. Cells were harvested for RNA sequencing (RNA-seq) after 20 days.

2024-11-29 | E-MTAB-14444 | biostudies-arrayexpress

Crohn's Disease patients and non-IBD controls : ileal gene expression

Project description:Comparison of gene expression from ileal biopsies of Crohn's Disease patients and non-IBD controls

2022-12-30 | E-MTAB-10395 | biostudies-arrayexpress

Mapping effective microRNA pairing beyond the seed using abasic modifications

Project description:MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by base-pairing to complementary sites in mRNAs. The primary element for site recognition is the seed region (nucleotides 2-8 in the miRNA), but for a minority of sites pairing outside the seed increases efficiency, with the supplementary region (nucleotides 13-16) typically having the greatest impact. However, the structural determinants of effective pairing outside the seed are not fully understood. Here, we use abasic modified nucleotides to disrupt pairing to residues 13 and 14 of miR-34a and measure the effect of this modification compared to wild-type miR-34a on the cellular transcriptome and proteome using RNA-seq and mass spectrometry. We find that a subset of sites with predicted supplementary pairing are affected by miRNA transfection, with up to two-fold decreases in site repression at the mRNA level, although the effect at the protein level is less pronounced. Overall, this study demonstrates a novel methodological approach for elucidating the role of specific miRNA residues in target site selection, advancing our understanding of miRNA-mediated gene regulation.

2025-05-07 | PXD059550 | Pride

Enhanced capacity to dissipate body heat alters mammary gene expression in lactating mice

Project description:The experiment was performed on 10 lactating laboratory mice (Mus musculus, MF1). Half of the mice were shaved to increase their capacity to dissipate body heat (and thus milk production), while the other half were unshaved controls. By RNA-seq profiling of the mammary gland in shaved and unshaved lactating mice, we identified differentially expressed genes (DEGs) associated with shaving and then compared them with three sets of genes compiled from the mouse mammary gland literature, containing 1) imprinted genes, 2) milk synthesis-related genes, and 3) involution-related genes. Finally, DEGs induced by shaving were subjected to functional analysis of gene expression, with the focus on canonical pathways, upstream regulators, and downstream effects. We demonstrated that the shaving-induced increases in milk production were not associated with the changes in the expression of imprinted or milk-synthesis related genes. Instead, several lines of evidence strongly suggest that the mammary gland of shaved mice went into involution earlier than that of unshaved mice. Our interpretation of these results is that once provided with the enhanced capacity to dissipate body heat, shaved mice were able to rear their young to independence faster than unshaved mothers, benefiting potentially from shorter lactation and shorter interbirth interval to maximise their lifetime reproductive success.

2022-12-31 | E-MTAB-11654 | biostudies-arrayexpress

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