Biology and Therapeutic Targeting of Malignant Monocytes in Myeloid Blood Cancers
Abstract
Fiscal Year 2020 (FY20) Peer Reviewed Cancer Research Program (PRCRP) Topic Area(s) and Military Health Focus Area(s) to be addressed by the research project: This proposal is focused on FY20 PRCRP Topic Area of blood cancers. This proposal addresses several Military Health Focus Areas, including: (i) environmental risk factors associated with blood cancer development (Aim 1), (ii) gaps in blood cancer prevention, early detection/diagnosis, prognosis, and treatment (Aims 1, 2, 3). Scientific Objective and Rationale for the Proposed Project: This proposal is focused on a type of white blood cell called monocytes. We have found that having an abnormally increased number of monocytes in the blood is associated with a reduced lifespan in individuals who don’t have blood cancers. It has been previously found that having an abnormally increased number of monocytes in certain blood cancers is associated with a poor prognosis. Finally, there is a blood cancer that causes monocytes to grow abnormally. It is called chronic myelomonocytic leukemia and has a very poor prognosis. For all these reasons, we decided to focus on studying monocytes in blood cancers. The scientific objective is to understand how certain gene mutations (i.e., in ASXL1, SRSF2, and JAK2) alter monocytes and cause them to grow abnormally to cause blood cancers and also to develop new ways to target abnormal monocytes in blood cancers. Describe the near-term impact for patients and ultimate applicability of the research: There are several opportunities for near-term impact for patients with blood cancers: (i) Developing a clinical trial in a particular type of blood cancer called MPN (myeloproliferative neoplasms) using a drug called Elo (elotuzumab) that kills monocytes (ii) Identifying environmental factors that could be modified to prevent the development of blood cancers, e.g., toxic exposures, lifestyle factors (iii) Establishing new biological markers (biomarkers) to identify patients with blood cancers who are at higher risk of progression and therefore, should be treated sooner (iv) Advancing the understanding of how these difficult-to-treat blood cancers are caused, with the goal of coming up with entirely new ideas about how to target them, and to develop new clinical trials What types of patients will it help, and how will it help them? (1) It will help people who are at risk of developing a blood cancer but don’t yet have it by identifying changes in lifestyle that can help prevent cancer, and possibly medical treatments to take to prevent blood cancer; (2) It will help people who already have blood cancers through the development of earlier treatments to prevent their cancer from progressing; (3) It will help people who already have blood cancers through the development of entirely new approaches to treat their cancer. What are the potential clinical applications, benefits, and risks? Clinical applications include clinical trials of new treatments and new biomarkers to identify risk of progression. Benefits are increased understanding of how these cancers develop and new ways to prevent/treat them. The risks are minimal. Patients are asked to donate blood for research when they are having a lab draw already. What is the projected time it may take to achieve a patient-related outcome? Within 3 years, possibly sooner. What are the likely contributions of this study to advancing at least one of the FY20 PRCRP Topic Area? We believe our proposal will have a major positive impact on blood cancers in the near term. Describe how the proposed research is relevant to active-duty Service Members, Veterans, and military: Cancer takes a high toll on Veterans, active military, and their beneficiaries. There are several reasons for this including toxic environmental exposures (e.g., radiation); lifestyle factors such as smoking; the effects of aging; and the impact of treatments for other cancers (e.g., lung cancer)
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110909
Entities
People
- Ann Mullally
Organizations
- United States Army