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Garcia-Manero, Guillermo, M.D.

Researcher Profiles

Researcher Profiles

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Guillermo Garcia-Manero, M.D.

Guillermo Garcia-Manero, M.D.

University of Texas M. D. Anderson Cancer Center

2021 Funding recipient

Targeting IL1-Beta in clonal cytopenia of undetermined significance and low-risk myelodysplastic syndromes

Discovery Research Grant 2021

PROJECT SUMMARY

ging can be associated with alterations in the production of the different cells that compose the blood. These changes can manifest as anemia, due to a decreased number of red cells; leukopenia, related to a decrease in white blood cells; and thrombocytopenia, due to a decreased number of platelets. Clinically, these blood deficiencies translate into symptoms of fatigue, increased risk of infections, and bleeding. As we age, the bone marrow stem cells that give rise to all the different cells in the blood can acquire genetic mutations. Initially, these mutations can start by affecting only small populations of marrow cells, a process known as clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS). Over time, and under pressure from other factors, such as inflammation or chemotherapy used to treat other cancers, these CHIP/CCUS clones can expand and develop into a type of leukemia, known as myelodysplastic syndrome (MDS). In our laboratory, we search to understand how CHIP progresses to MDS with the main goal of developing clinical strategies to stop this process. In previous work in our laboratory, we found that these mutant cells in the bone marrow produce very high levels of a protein known as interleukin 1b (IL1b). We believe that this protein can provide an advantage to the mutant cells and kill the normal ones. Over the last 2 years, we dissected the effects of an inhibitor of IL1b, known as canakinumab, on bone marrow function. In this proposal, we plan to study the cellular and molecular effects of canakinumab in the bone marrow of patients with CHIP/CCUS and low-risk MDS enrolled in a clinical trial of canakinumab. The results of these studies will have a major impact on our understanding of the role of IL1b in bone marrow function and could also lead to new preventive and treatment approaches for individuals with CHIP/CCUS and MDS.

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