There are many different forms of leukemia. Acute lymphoblastic leukemia (ALL) is a relatively common form of leukemia affecting children and adults of all ages. Although most patients with ALL will be cured, many patients still do poorly, and many survivors also experience long-term adverse effects of chemotherapy, such as impaired growth, infertility, and the risk of secondary cancers. Therefore, more effective, less toxic therapies are needed. In our preliminary work, we have uncovered a new pathway important to the stem cells that control ALL growth and disease progression. In this proposal, we aim to perform the necessary studies to determine if targeting this pathway is a feasible way to treat ALL.

Dr. Grant Rowe is a new principal investigator in hematology and oncology at Boston Children’s Hospital and Harvard Medical School. His long-term goal is to become an expert in normal and diseased blood stem cells, with the aim of translating findings from his research laboratory into new therapies. This proposal pursues this long-term goal: the objective is to translate preliminary research on fundamental aspects of the stem cells in ALL into a new approach to treatment. Support from the Department of Defense will provide key support in achievement of this long-term goal by protecting time and effort for this research, expanding Dr. Rowe’s network of collaborators through the Virtual Cancer Center, and supporting the career development plan.

The ultimate applicability of this work is to translate our basic work on the stem cells of ALL into a new approach to treatment. Upon completion of this study, we expect to have completed the preclinical research (i.e., animal-based studies) necessary to justify planning early phase human trials targeting metabolism in ALL stem cells. Advancement of a new therapeutic approach would have the potential to first help patients with treatment-resistant or relapsed ALL as these patients are often enrolled in early phase studies. We expect that since our main proposed treatment agent – tigecycline – is approved by the Food and Drug Administration as an antibiotic, early phase studies will demonstrate safety of this agent for use in ALL patients. If this new treatment shows potential efficacy in early phase studies, it could be moved into upfront treatment regimens where it has the potential to impact the 12,000 people diagnosed with ALL in the United States each year. The process of studying the safety and efficacy of a new cancer drug can require 5-10 years of clinical trials, and so presenting a strong preclinical rationale for such an investment of time – as we expect that we will – through rigorous basic research study is crucial. At a basic research level, we expect that the new biology related to leukemic stem cells that we uncover will have broad impact and potential translation to other forms of leukemia.

Since ALL afflicts humans of all ages, we expect that completion of the proposed research and its translation into future clinical trials will broadly benefit active duty Service members, Veterans, and other military beneficiaries.