Leukemia is a debilitating blood cancer that can occur in childhood or throughout life and is particularly lethal in older populations. Leukemia is a complicated disease to target because blood cells are constantly turned over, which in turn requires frequent regeneration and means mutations can occur that could lead to leukemia. The Resar lab at Johns Hopkins University School of Medicine, led by Dr. Linda Resar, is working on a molecular switch that can control the proliferation of blood cells. They hope that by modulating levels of this protein, they can improve healthy cell growth while weakening leukemic cells.
To learn more about the Maryland Stem Cell Research Fund (MSCRF), visit www.mscrf.org.
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Background:
Blood cell production is particularly susceptible to mutagenesis due to the constant need to regenerate new blood cells. Mutagenesis of blood-forming tissues can lead to diseases like blood cancer, including leukemia. In leukemia, mutagenesis of the blood cells leads to uncontrolled growth and malfunctioning blood cells. Leukemia is diagnosed in thousands of children a year and hundreds of thousands of patients worldwide. While different forms of leukemia may weaken the body to varying levels, leukemia is highly lethal when it occurs in older patients. Current treatment for rapidly progressing leukemia is primarily chemotherapy, which is also high-risk in older patients. Therefore, developing treatments should provide means to prevent leukemic cell proliferation while allowing healthy blood regeneration.
The Resar lab at Johns Hopkins University School of Medicine is researching the molecular determinants of blood cell proliferation to find ways to shift blood regeneration to favor healthy hematopoiesis (blood cell reproduction). Previous work from Dr. Linda Resar and her group identified high mobility group A chromatin regulator (HMGA1) as a highly produced factor in stem cells. HMGA1 is partly responsible for the ability of stem cells to self-replicate. However, HMGA1 is highly upregulated in stem cells during their transformation to a cancerous state, such as leukemia. HMGA1 is a significant modulator that, when controlled, could dampen leukemic cell growth or enhance healthy hematopoiesis.
In work supported by the Maryland Stem Cell Research Fund (MSCRF), the Resar lab is building upon their previous research by using CRISPR, a relatively new genetic engineering technology, to tune the expression of HMGA1 to do just that. By turning down HMGA1 levels in cancerous cells, they will no longer be able to replicate and over-populate. Additionally, stem cells may be damaged during chemotherapy, leading to a decrease in HMGA1 levels. By upregulating HMGA1 levels in stem cells that have suffered from radiation or other injuries, the Resar lab hopes to enhance stem cell performance and, in turn, blood regeneration. The Resar lab is leveraging MSCRF support to identify new therapies to prevent leukemia and other forms of cancer, which will prevent the deaths of elderly patients and allow children suffering from childhood diseases to live healthier and fuller lives.
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4 окт 2022
