ArticleHaematologica2015
Hematopoiesis specific loss of Cdk2 and Cdk4 results in increased erythrocyte size and delayed platelet recovery following stress.
Article in Haematologica, 2015. 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
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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, 33 citations in OpenAlex.
- EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis.Nature communications · 2021Trial
- FOXO1 Integrates Endothelial Hemodynamic, Inflammatory, and Metabolic Pathways in Atherosclerosis.Circulation research · 2026Article
- Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.Expert opinion on therapeutic targets · 2025Review
- Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.Journal of advanced research · 2025Review
- RHOB regulates megakaryocytic and erythroid differentiation by altering the cell cycle and cytoskeleton.Scientific reports · 2025Article
- cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling.Science advances · 2025Article
- Monitoring the Response of Cyclin-Dependent Kinase 4/6 Inhibitors with Mean Corpuscular Volume.Current oncology (Toronto, Ont.) · 2024Article
- Article
- A curious case of cyclin-dependent kinases in neutrophils.Journal of leukocyte biology · 2022Review
- Inducible deletion of CDK4 and CDK6 - deciphering CDK4/6 inhibitor effects in the hematopoietic system.Haematologica · 2021Article
- CDK2 limits the highly energetic secretory program of mature β cells by restricting PEP cycle-dependent KCell reports · 2021Article
- Phenotypical microRNA screen reveals a noncanonical role of CDK2 in regulating neutrophil migration.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- CDK2 regulates the NRF1/The Journal of cell biology · 2019Article
- How to expel a bad tenant: Linking cyclin A2, enucleation and cell size.Cell cycle (Georgetown, Tex.) · 2017Article
- Loss of Cyclin-dependent Kinase 2 in the Pancreas Links Primary β-Cell Dysfunction to Progressive Depletion of β-Cell Mass and Diabetes.The Journal of biological chemistry · 2017Article
- Cyclin A2 regulates erythrocyte morphology and numbers.Cell cycle (Georgetown, Tex.) · 2016Article
- Cell cycle regulation of hematopoietic stem or progenitor cells.International journal of hematology · 2016Review
- Quo Vadis Cell Growth and Division?Frontiers in cell and developmental biology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mouse knockouts of Cdk2 and Cdk4 are individually viable whereas the double knockouts are embryonic lethal due to heart defects, and this precludes the investigation of their overlapping roles in definitive hematopoiesis. Here we use a conditional knockout mouse model to investigate the effect of combined loss of Cdk2 and Cdk4 in hematopoietic cells. Cdk2(fl/fl)Cdk4(-/-)vavCre mice are viable but displayed a significant increase in erythrocyte size. Cdk2(fl/fl)Cdk4(-/-)vavCre mouse bone marrow exhibited reduced phosphorylation of the retinoblastoma protein and reduced expression of E2F target genes such as cyclin A2 and Cdk1. Erythroblasts lacking Cdk2 and Cdk4 displayed a lengthened G1 phase due to impaired phosphorylation of the retinoblastoma protein. Deletion of the retinoblastoma protein rescued the increased size displayed by erythrocytes lacking Cdk2 and Cdk4, indicating that the retinoblastoma/Cdk2/Cdk4 pathway regulates erythrocyte size. The recovery of platelet counts following a 5-fluorouracil challenge was delayed in Cdk2(fl/fl)Cdk4(-/-)vavCre mice revealing a critical role for Cdk2 and Cdk4 in stress hematopoiesis. Our data indicate that Cdk2 and Cdk4 play important overlapping roles in homeostatic and stress hematopoiesis, which need to be considered when using broad-spectrum cyclin-dependent kinase inhibitors for cancer therapy.
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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.