ArticleLeukemia2022
A senescence stress secretome is a hallmark of therapy-related myeloid neoplasm stromal tissue occurring soon after cytotoxic exposure.
Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 19 citations in OpenAlex.
- Second primary cancers following hematologic malignancies: Epidemiology, pathobiology and clinical management.Human vaccines & immunotherapeutics · 2026Review
- Article
- Injury-driven stromal exhaustion disrupts intrinsic regenerative capability.Nature communications · 2026Article
- SIRT6-Mediated Deacetylation of ATF3 Promotes Silica-Induced Lung Fibrosis by Enhancing its Nuclear Import via Binding to Importin α.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia.Biomedicines · 2026Review
- Beyond biochemical cascades: novel bio-mechanical and epigenetic paradigms of glial SASP in brain aging.Metabolic brain disease · 2026Review
- DNA hydroxy methylases Tet1 and Tet2 regulate bone aging and bone marrow stromal cell metabolism through the IGF-1/mTOR signaling axis.Stem cells (Dayton, Ohio) · 2025Article
- Review
- Therapy-Related Myeloid Neoplasms: Complex Interactions among Cytotoxic Therapies, Genetic Factors, and Aberrant Microenvironment.Blood cancer discovery · 2024Review
- Senescence in the bone marrow microenvironment: A driver in development of therapy-related myeloid neoplasms.Journal of bone oncology · 2024Article
- Therapy-Related Myeloid Neoplasm: Biology and Mechanistic Aspects of Malignant Progression.Biomedicines · 2024Review
- Special Issue "Advances in Molecular Pathogenesis and Targeted Therapies for Myeloid Neoplasms".International journal of molecular sciences · 2024Article
- RAB27B-regulated exosomes mediate LSC maintenance via resistance to senescence and crosstalk with the microenvironment.Leukemia · 2024Article
- The immunome of mobilized peripheral blood stem cells is predictive of long-term outcomes and therapy-related myeloid neoplasms in patients with multiple myeloma undergoing autologous stem cell transplant.Blood cancer journal · 2023Article
- TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms.Blood cancer journal · 2023Article
- Review
- Cellular microenvironment: a key for tuning mesenchymal stem cell senescence.Frontiers in cell and developmental biology · 2023Review
- Bone Marrow Microenvironment Involvement in t-MN: Focus on Mesenchymal Stem Cells.Mediterranean journal of hematology and infectious diseases · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapy-related myeloid neoplasm (tMN) is considered a direct consequence of DNA damage in hematopoietic stem cells. Despite increasing recognition that altered stroma can also drive leukemogenesis, the functional biology of the tMN microenvironment remains unknown. We performed multiomic (transcriptome, DNA damage response, cytokine secretome and functional profiling) characterization of bone marrow stromal cells from tMN patients. Critically, we also compared (i) patients with myeloid neoplasm and another cancer but without cytotoxic exposure, (ii) typical primary myeloid neoplasm, and (iii) age-matched controls to decipher the microenvironmental changes induced by cytotoxics vs. neoplasia. Strikingly, tMN exhibited a profoundly senescent phenotype with induction of CDKN1A and β-Galactosidase, defective phenotype, and proliferation. Moreover, tMN stroma showed delayed DNA repair and defective adipogenesis. Despite their dormant state, tMN stromal cells were metabolically highly active with a switch toward glycolysis and secreted multiple pro-inflammatory cytokines indicative of a senescent-secretory phenotype that inhibited adipogenesis. Critically, senolytics not only eliminated dormant cells, but also restored adipogenesis. Finally, sequential patient sampling showed senescence phenotypes are induced within months of cytotoxic exposure, well prior to the onset of secondary cancer. Our data underscores a role of senescence in the pathogenesis of tMN and provide a valuable resource for future therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.