Investigating the Mechanisms of Leukemia Initiation in the Context of Obesity
Abstract
Rationale: Studies have shown that obesity is a significant risk factor for blood cancers. Obese persons have a greater risk of developing the disease and their treatment is more difficult. However, despite its clinical relevance, little is known about how obesity affects the development of leukemia. Obesity is a complex condition primarily defined by the excessive accumulation of fat cells. These cells mainly serve to store energy but also serve to produce a particular type of hormones called adipokines that regulate many important functions of the body. For example, one of them, leptin, is known to regulate appetite and fat storage. Another, adiponectin, is known to regulate production of sugars and lipids. The level of these adipokines in the body is profoundly dysregulated in overweight or obese persons. Interestingly, it has been shown that these adipokines also affect the activity of the hematopoietic stem cells, a pool of cells in the bone marrow that are responsible for the controlled production of all blood cells. These hematopoietic stem cells, when dysregulated, are at the root of most blood cancers. Based on this information, we propose that adipokines could regulate leukemia development and may constitute the missing link between obesity and leukemia. In this project, we will focus on myeloproliferative disorders, slow progressing diseases that naturally evolve into acute leukemia. We will work with mouse models that mimic human leukemia to determine how adipokines affect development of this disease. We will focus our study on the role of adiponectin and leptin and test the hypothesis that dysregulation of these adipokines during obesity specifically helps the growth of the leukemic cells at the expense of the normal blood cells. Goals in Cancer Research: My career goal is to develop an independent research program in the field of blood cancer research. Work in my laboratory focuses on dissecting how environmental signals regulate normal blood production and how disruption of these signals leads to leukemia. Our work especially explores how obesity can contribute to leukemia initiation. Funding from this Career Development Award will allow for the investigation of a new avenue of research focusing on the function of adipokines in disease development. This award and the guidance of my mentor during this project will also help me to develop my expertise in the field as well as to establish new tools and protocols to explore these questions. Contributions to the Field of Cancer Research: I believe that completion of the proposed project will help us to better understand the link between obesity and leukemia. It will show how the adipokine imbalance provoked by obesity could favor the growth of abnormal hematopoietic stem cells at the expense of the normal ones. This knowledge can be translated into the development of new adipokines-targeting therapies that could be used for overweight or obese patients suffering from myeloproliferative disorders and other blood cancers. Impact on Military Beneficiaries: The obesity epidemic has particularly affected the Veteran population with 70% of Veterans being overweight or obese. This phenomenon has been linked to eating disorders associated with post-traumatic stress disorder or to simple changes of lifestyle after military discharge. As such the established link between obesity and blood cancers constitutes a particular concern for military personnel, Veterans, and their families. This work will advance our knowledge about the role of leptin and adiponectin in leukemia initiation and development. By analyzing the mechanism linking obesity and leukemia initiation, we hope to identify new potential therapeutic targets and eventually provide new treatment options for overweight or obese patients affected by leukemia.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510344
Entities
People
- Damien Reynaud
Organizations
- United States Army