Nadia Carlesso talks inflammation and the MPNs
Inflammation and the MPNs
Nadia Carlesso MD, PhD, has been having a good summer. In July she was published in Cell, a scholarly journal, for her work identifying the events leading to inflammation in the bone marow. A few days later, MPN Research Foundation awarded her $100,000 to expand upon this work in a project for the MPN Challenge. We asked Dr. Carlesso about the role of inflammation in the progression to myelofibrosis, and what we can expect from her project.
MPNRF: Dr. Carlesso, please tell us what you are hoping to learn from the MPN Challenge grant in the short and long term.
NC: At short-term we will use these resources to study directly bone marrow samples from MPN patients to determine whether their bone marrow stroma present an inflammatory phenotype. Our long-term objective is to use the animal models we developed to more precisely determine the mechanisms by which inflammation contributes to fibrosis, bone marrow failure and leukemia transformation and to test new drugs.
MPNRF: Can you describe the role immunotherapy plays in your project?
NC: Our findings suggest that inflammation plays a critical role in the development of MPN. Ultimately there is a complex network of different cell types in the bone marrow involved in generating or propagating inflammation, including cells of the innate immune system. Thus, targeting the inflamed microenvironment, in addition to targeting the tumor cells, should provide a more effective therapy to prevent MPN disease progression.
MPNRF: Why is research into the bone marrow environment important to understanding and treating myelofibrosis?
NC: We know that there is an intricate relationship between the tumor cells and the stromal cells of the bone marrow microenvironment, which results in the marrow fibrosis. However, the precise cellular and molecular mechanisms that underlie the bone marrow stromal changes are incompletely understood. A better understanding of the role of bone marrow microenvironment stromal cells is critical to develop therapeutic approaches to prevent or minimize marrow fibrosis.
MPNRF: What other pivotal discoveries on the role of the niche have been made in recent years?
NC: In recent years further evidences were provided supporting the idea that different cellular niches in the bone marrow contribute to the development and homeostasis of different blood cell lineages, an important advance to better understand normal and malignant hematopoiesis. Furthermore, several studies have shown that the marrow microenvironment can directly contribute to leukemias, and that the sympathetic nervous system plays a role in regulating normal and malignant blood cells formation.