Role of the Aged Bone Marrow Microenvironment in Modulation of Hemapoietic Failure and Transformation in Myelodysplastic Syndrome
Technical Report,01 Sep 2018,31 Aug 2019
University of Rochester Rochester United States
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Our research focus is on ways in which the cells and tissues supporting blood forming stem and progenitor cell can be rallied to improve blood count, 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 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 myelodysplastic syndromes, 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 if pharmacologic modulation of scavenger function could be a way to treat marrow failure. This is critical because patients with myelodysplastic syndrome 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, and it is therefore very innovative.
- Medicine and Medical Research
- Anatomy and Physiology