Role of the Aged Bone Marrow Microenvironment in Modulation of Hematopoietic Failure and Transformation in Myelodysplastic Syndrome
Abstract
Our research focus is on ways in which the cells and tissues supporting blood-forming stem and progenitor cells can be rallied to improve blood count and prevent marrow failure and transformation to acute leukemia. For several years, the core of our research team has been studying the microenvironment in the context of normal marrow function, aging, and blood cancers. Recently, we have discovered that the professional scavenger cells in the bone marrow of aged mice play a critical role in instructing all other microenvironmental populations, and together they can change the function of stem cells that produce blood. To study this process and whether it plays a role in marrow failure, we recruited an expert in these scavenger populations. Together, we were able to show that aged and myelodysplastic syndromes (MDS) scavenger cells have a significant defect in engulfing dying cells in the marrow. This is very important because dying cells that are not taken up by scavenger cells release inflammatory signals in their vicinity that can disrupt normal production of blood cells and even accelerate transformation to leukemia. In fact, it is known that, in marrow failure due to MDS (the disease we are studying), there is a great increase in programmed cell death in the marrow. In this proposal, we seek to use mouse models where the scavenger function is increased or decreased and induce marrow failure to see whether pharmacologic modulation of scavenger function could be a way to treat marrow failure. This is critical because patients with MDS are primarily elderly and often are not candidates for bone marrow transplantation, the curative treatment for this disease. Our results will add a complete new class of treatments that focus on the contribution of the cells and tissues supporting the blood-forming cells; therefore, it is very innovative. Since there are pharmacologic ways to modulate scavenger function, this idea, if supported by data generated by this proposal, has a strong potential to be translated to the clinic.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810485
Entities
People
- Laura Calvi
Organizations
- United States Army
- University of Rochester