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Researchers discover a small molecular inhibitor with big potential for children with mixed lineage leukemia (MLL).
Leukemia is the most common cancer in children and teens, accounting for almost 1 out of 3 cancers. Most childhood leukemias are acute types—acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). Survival rates for these acute leukemias have improved over time.
However, certain subtypes of these blood cancers have features of both ALL and AML, and with both genetic and nongenetic changes, that make identifying effective treatments difficult.
One subtype that is particularly aggressive and prevalent in infant leukemias is called mixed lineage leukemia (MLL). More effective therapies are urgently needed for MLL patients because chemotherapy does not work effectively against it, and the 5-year survival rate is only approximately 35%.
Jolanta Grembecka, PhD, and colleagues are developing new therapies for MLL leukemia, which is caused by a genetic defect involving MLL1 gene that fuses with other genes to result in hybrid proteins that fuel cancer growth.
Grembecka’s lab focuses on the discovery and development of small molecules for targeted therapies in cancer. (She is the inventor on 13 patents.) These treatments use drugs to block the growth and spread of cancer by interfering with proteins involved in the cancer’s growth (cell division) and its spread. By targeting specific proteins, these treatments are more effective and less harmful to normal blood cells than chemotherapy and radiation.
With financial support through a research grant from the American Cancer Society (ACS), Grembecka’s team has been developing and testing drugs in mice that specifically target MLL1 fusion proteins in acute leukemias.
Their new drug (MI-3454) inhibits the ability of a critical protein called menin to interact with these fusion proteins, and their results have proven fruitful in mice with MLL leukemia, according to a recently published study in The Journal of Clinical Investigation.
Grembecka’s research team is also testing their menin inhibitors together with drugs that specifically target other molecular defects in aggressive leukemias. As they predicted, this combination approach has led to more complete and long-lasting remission of leukemia in mice.
Grembecka’s pre-clinical successes provided a path for a phase 1 clinical studies with menin inhibitors in children and adults with certain types of acute leukemia.
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