Studying the genome of different organisms leads to the discovery of many different cellular processes and how certain phenotypes are influenced. Whenever I think about mutations or alterations in gene expression I immediately think of diseases. Genetic research does lead to the understanding of different diseases, but it also leads to knowledge on how to treat these disorders. Once scientists are able to narrow down the genes and specific gene functions that influence a particular disease, they can then work at finding a way to alter gene regulation in order to treat the disease. The study of Acute Myeloid Leukemia (AML) is an example of how scientists have taken what they know about gene expression in order to treat individuals with the disease.
Acute Myeloid Leukemia is a disease where underdeveloped blasts grow within the bone marrow and peripheral blood as a result of the cell's inability to differentiate (Ma et. al, 2014). Ma et. al (2014) explains how, "FMS-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that is expressed in stem cells." When FLT3 binds it results in the activation of phosphorylation of proteins and also triggers other pathways within the cells (Ma et. al, 2014). A mutation occurs in individuals with Acute Myeloid Leukemia where FLT3 is activated without having to be bound to the ligand (Ma et. al, 2014). There are a couple different mutations that have been found to affect FLT3, but the most widely known case is when there is an internal replication of different lengths of the sequence (Ma et. al, 2014). This activation allows for continued growth of the cells which is seen in Acute Myeloid Leukemia. Ma et. al (2014) as well as other scientists are trying to find something that will inhibit FLT3 in order to treat individuals with this disease. Currently TTT-3002 is under observation as a possible new inhibitor that may be able to treat Acute Myeloid Leukemia (Ma et. al, 2014). Ma et. al (2014) believe that TTT-3002 prevents FLT3 activity by producing mutations on residue D835. TTT-3002 has been tested in mice, and so far, has been able to inhibit FLT3 containing multiple mutations, as well as working against blasts within the bone marrow and blood that express FLT3 (Ma et. al, 2014). It seems to be the strongest acting treatment to date that does little harm to the host (Ma et. al, 2014). This occurs as a result of TTT-3002's selectivity to FLT3 allowing it to more directly reach the target intended. Although this inhibitor is predicted to hold up against resistance from FLT3, studies have recorded that its effects are more damaging when doses are paired with chemotherapy (Ma et. al, 2014). TTT-3002 has more promising effects on Acute Myeloid Leukemia when it is the sole treatment. Trials on human patients are now under way, but there is still much research that needs to be done on this inhibitor and its capability to treat Acute Myeloid Leukemia.
It’s great that scientists are looking to the physical organism, rather than synthetic medicines, to try and combat cancers. I must confess to being rather daunted by all the terminology they use! What, exactly is TTT-3002? You say it is an inhibitor but how does it work I the body?
ReplyDeleteTTT-3002 is a compound that is ingested orally. I don't know exactly how the drug was made, but scientists are still currently researching its affects. The FLT3 is permanently turned on in people with Acute Myeloid Leukemia. This causes leukemia stem cells to continually be reproduced. TTT-3002 targets this receptor and prevents further proliferation of stem cells. Research also suggests that TTT-3002 is able to target other proteins that act along the same pathway as FLT3 and inhibit their activity as well. The targeting ability of this drug may allow it to treat even certain resistant strains of Acute Myeloid Leukemia.
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Johns Hopkins Medicine 2014, 'Experimental Drug Shows Promise for Treatment-Resistant Leukemias,' Newswise, viewed 23 March 2014,.
http://www.newswise.com/articles/experimental-drug-shows-promise-for-treatment-resistant-leukemias
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