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Leukemias are a type of cancer that occurs in blood cells, and they are the most common types of cancer in children. T-cell acute lymphoblastic leukemia (T-ALL) occurs when immune cells called thymocytes become cancerous. There’s also a rare and aggressive form of T-ALL called Early T-cell Precursor ALL (ETP-ALL) that is hard to treat. Scientists know that a protein called Lmo2 can be responsible for driving these transformations in thymocytes, but they don’t know precisely how this occurs.
The Love Lab demonstrated that the protein Ldb1 helps drive the development of T-ALL and ETP-ALL in mice. They examined the role of Ldb1 by deleting it from a mouse model of T-ALL and ETP-ALL. Even though Lmo2 was present, thymocytes were not able to proliferate aggressively without Ldb1, and they resembled normal, healthy cells. Mice that should have otherwise developed T-ALL or ETP-ALL did not become sick, and other genes that are typically overactivated in this type of cancer remained at normal levels. The findings suggest that Ldb1 is essential for Lmo2-driven leukemia.
The study team also conducted additional experiments to determine how Ldb1 works with Lmo2. Their research suggests that Ldb1, which is a nuclear adaptor protein, likely forms a transcription complex with Lmo2 (and possibly other unidentified proteins) to turn on genes necessary for the cell to renew itself. This is a healthy feature of thymocytes under normal circumstances. But when Lmo2 is overexpressed, its complex with Ldb1 does not turn off, and the cell replicates unchecked. Thus, these thymocytes are predisposed to become cancerous and can eventually result in T-ALL and ETP-ALL. If the lab’s findings are replicated in people, targeting Ldb1 may be a promising therapy to treat ETP-ALL.
Learn more about the Genetics and Epigenetics of Development Group: https://www.nichd.nih.gov/about/org/dir/affinity-groups/GED.
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