“This new work from Gaertner et al. is significant and potentially field-changing,” says Anandi Krishnan PhD from Rutgers University, commenting on the new Nature journal study. “This is especially relevant in the context of managing blood disorders such as MPNs.”
The study does not mention ‘cancer’ or ‘myeloproliferation,’ yet its findings may be crucial for controlling essential thrombosis (ET), a type of myeloproliferative neoplasm (MPN).
Not So Basic Research
There are several ways to categorize biological research. Translational research aims to understand the broken systems behind disease states and potential treatments. In contrast, basic research is science in its simplest form, attempting to answer the question, “how does this work?” It seeks to uncover fundamental operations or principles without considering diseases or treatments.
However, biology is inherently interconnected and frequently resists simple categorization. At every level, systems spill over and blur with one another, even when it comes to research applications. While basic science research establishes a bedrock of understanding, it can also have a far-reaching impact and sometimes jumps ahead of translational research’s current understanding of a disease.
The study Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis, published in Nature, exemplifies basic science generating new research questions and possibilities. Although not a cancer study, the implications are proliferative.
The Basics of Platelet Production
Platelets are tiny blood cells crucial for blood clotting. They are born from the destruction of large megakaryocyte cells (MKs). When creating platelets, MKs grow four-times their size as they rapidly copy their DNA and invaginate their internal membranes. Eventually, the MKs burst or seep DNA fragments and 2,000 to 5,000 soon-to-be platelet cells into the bloodstream. This entirely consumes the MKs, requiring the formation of new replacement MKs through the process of megakaryopoiesis.
Key Discovery: The Role of Immune Cells
Led by Dr. Gaertner and colleagues at University Hospital, LMU Munich, the researchers describe how plasmacytoid dendritic cells (pDCs) of the immune system play a crucial role in balancing bone marrow activity. “Their discovery of pDCs as key regulators in megakaryopoiesis adds a new layer to our understanding of the role of the immune system in hematopoiesis, particularly platelet production and maintenance,” explains Krishnan, who was not directly involved with the research but was the recipient of a 2021 MPN Challenge™ award.
MKs, in green, are closely monitored by pDCs, whose movements are tracked here over time. CC by 4.0
The data suggests that pDCs slowly patrol the bone marrow, sticking close to MKs. When they sense the DNA expelled by terminal megakaryocytes, pDCs release a substance called interferon-alpha (IFNα), which signals the bone marrow’s stem cells to produce more megakaryocytes. This ensures a future supply of platelets. Managing the balance of blood cell production –hematopoiesis– in the bone marrow ensures that platelet production can ramp up during times of need, such as injury or illness.
Why This Matters: Potential for New Treatments
“Their study highlights the specific role of type 1 interferons in influencing hematopoietic processes,” explains Krishnan. She sees the connection between this basic research discovery and how it translates to her own interests in oncology. “This is especially relevant in the context of managing blood disorders such as MPNs, and yes, could open up new therapeutic avenues for ET, where abnormal platelet counts, and platelet dysfunction is noted.”
The Gaertner et al. findings revealed an on-off switch for platelet production. Targeting the immune signal or pDCs could prove useful for treating patients with ET, who produce too many platelets.
Beyond Platelets
If measured by the number of new applications or inspired hypotheses, the Gaertner et al. paper is a great success. This study underscores the value of basic research, where scientists explore fundamental questions without immediate applications in mind. These explorations are important to fund as they often spark breakthroughs and inspire transformative research.
Innovative scientists across the fields of oncology and immunology are likely to build off this basic research towards translational pursuits. By identifying a cell responsible for monitoring a specific niche of the bone marrow’s cell factory, this study will likely lead to creative ways to correct platelet production.
Sources: Megakaryopoiesis and Thrombopoiesis (youtube.com)
Gaertner, F., Ishikawa-Ankerhold, H., Stutte, S., Fu, W., Weitz, J., Dueck, A., Nelakuditi, B., Fumagalli, V., van den Heuvel, D., Belz, L., Sobirova, G., Zhang, Z., Titova, A., Navarro, A. M., Pekayvaz, K., Lorenz, M., von Baumgarten, L., Kranich, J., Straub, T., … Massberg, S. (2024). Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis. Nature, 631(8021), 645–653. https://doi.org/10.1038/s41586-024-07671-y
Correspondence with Dr. Anandi Krishnan
Certain medicines listed may not be approved by the US Food and Drug Administration (FDA) for myelofibrosis but are recommended by the National Comprehensive Cancer Network (NCCN). MPN Research Foundation works with NCCN on the creation and updating of its MPN Patient Guidelines.