Evidence map›Paper›PMID 39320136›Full record

ArticleCancer medicine2024

Unraveling the impact of lysosomal dysfunction on myeloproliferative neoplasm.

Hyundong Yoon, Dohoon Lee, Seulki Song, Bonil Koo, Jihyun Park, Tae Kon Kim, Sun Kim, Sheehyun Kim, Junshik Hong, Ja Min Byun and 4 more

Abstract read
In one paragraph

Article in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Hyundong YoonCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Dohoon LeeBioinformatics Institute, Seoul National University, Seoul, Republic of Korea.
Seulki SongCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Bonil KooInterdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0003-4357-1850
Jihyun ParkCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Tae Kon KimDivision of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Sun KimInterdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea.
Sheehyun KimDepartment of Genomic Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Junshik HongCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ja Min ByunCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Dong-Yeop ShinCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Inho KimCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Youngil KohCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0002-4750-931X
Sung-Soo YoonCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0003-2591-7459

Funding

Sanofi GZ201711800
6 · The paper itself

Abstract

backgroundLysosomal dysfunction (LD) impacts cytokine regulation, inflammation, and immune responses, influencing the development and progression of cancer. Inflammation is implicated in the pathogenesis of myeloproliferative neoplasm (MPN). With a hypothesis that LD significantly contributes to MPN carcinogenesis by inducing abnormal inflammation, our objective was to elucidate the pathophysiological mechanisms of MPN arising from an LD background.

methodsGenotyping of the LD background was performed in a cohort of MPN patients (n = 190) and healthy controls (n = 461). Logistic regression modeling, utilizing genotype data, was employed to estimate the correlation between LD and MPN. Whole transcriptome sequencing (WTS) (LD carriers = 8, non-carriers = 6) and single-cell RNA sequencing data (LD carriers = 2, non-carriers = 2, healthy controls = 2) were generated and analyzed.

resultsA higher variant frequency of LD was observed in MPN compared to healthy controls (healthy, 4.9%; MPN, 7.8%), with the highest frequency seen in polycythemia vera (PV) (odds ratio = 2.33, p = 0.03). WTS revealed that LD carriers exhibited upregulated inflammatory cytokine ligand-receptor genes, pathways, and network modules in MPNs compared to non-carriers. At the single-cell level, there was monocyte expansion and elevation of cytokine ligand-receptor interactions, inflammatory transcription factors, and network modules centered on monocytes. Notably, Oncostatin-M (OSM) consistently emerged as a candidate molecule involved in the pathogenesis of LD-related PV.

conclusionsIn summary, an LD background is prevalent in MPN patients and leads to increased cytokine dysregulation and inflammation. OSM, as one of the potential molecules, plays a crucial role in PV pathogenesis by impairing lysosomal function.

Indexed as

LysosomesMyeloproliferative DisordersAdultAgedCase-Control StudiesCytokinesFemaleGene Expression ProfilingHumansInflammationMaleMiddle AgedPolycythemia VeraSingle-Cell AnalysisCytokinescytokine dysregulationgermline variantlysosomal storage diseasemyeloproliferative neoplasmOncostatin‐M

Identifiers

PMID39320136
PMCPMC11423461

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.