A new study conducted at Hiroshima University has discovered a new non-oncogene that could potentially decrease relapse rates of CML after treatment with TKIs.
Chronic myelogenous leukemia, also known as chronic myeloid leukemia(CML) is a type of cancer that alters the myeloid cells or the stem cells that give rise to the red blood cells, platelets, and white blood cells in the bone marrow due to a mutated oncogene called BCR-ABL.
This mutation turns an ordinary stem cell into a CML cell which keeps on growing and dividing, accumulating in the bone marrow, and eventually, spill into the bloodstream. Over time, these cells in the bloodstream settle in different organs like the spleen and give rise to cancerous growths.
CML is a slow-growing tumor and thanks to recent advances in science, easily treatable cancer too. However, it has the potential for transforming into an acute type of leukemia, which is difficult to treat.
Treatment for CML
The mutated oncogene, BCR-ABL, alters the normal functioning of the stem cells through the production of an abnormal enzyme that is crucial for proper communication and growth of stem cells. This abnormal enzyme is a tyrosine kinase and it is responsible for permanently activating the signal transduction cascade that is, in turn, responsible for the growth of CML cells.
However, a class of drugs called tyrosine kinase inhibitors(TKIs) is found to be very beneficial in the treatment of CML, with a high number of patients going into remission after its use. This drug stops the miscommunication due to the abnormal tyrosine kinase and controls the progression of the disease, but unfortunately, it does not cure the patient.
Although TKIs target the CML cells and prevent the reproduction of active proliferative cancerous stem cells, they do not have any effect on the quiescent (cells that are neither in the replicating phase nor are the dead, just idle) cancerous stem cells. Over time, even after the proliferative cells have been killed off by TKIs, drug resistance is possible and these quiescent cells may reactivate, causing a relapse of CML.
How to prevent the relapse of CML?
These idle cells are not affected by the TKIs in any way, since they do not need tyrosine kinase for their functioning. These cells are just plainly present waiting to be reactivated. In the recent research performed by Kazuhito Naka, an associate professor from the Department of Stem Cell Biology of Hiroshima University’s Research Institute for Radiation Biology and Medicine and his team, it was found that a different non-oncogene gene was involved in the regulation of these quiescent or idle cells that could be targeted to prevent relapse of CML.
The oncogene-independent survival of CML stem cells spurred researchers in discovering other vulnerabilities in CML stem cells. Naka and his team found that CML stem cells were surviving in vivo with the help of the Gdpd3 gene and when the gene was disrupted in the animal models, the rate of relapse decreased significantly. This lipid encoding gene activates different signaling pathways allowing for the growth of idle cells and the researchers believe that it could be a new target for CML treatment and the treatment of other cancers, perhaps. However, they do not understand the exact mechanism and call for further research into Gdpd3 and its mechanism of action.
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