Study Finds Enzyme Linked to the Acceleration of Malignant Proliferation in CML
A new research led by scientists from the University of California, San Diego School of Medicine, reveals a new enzyme that is thought to play a key role in the process that aides the cloning of malignant stem cells, thus being directly involved in the evolution of CML (Chronic myeloid leukemia). CML is a type of cancer that affects the bone marrow and the blood. Researchers suggest that the prevalence of this type of cancer is increasing.
The paper was published in late December 2012, in the online edition of the journal Proceedings of the National Academy of Sciences. In spite of the recent therapies developed for CML and other leukemias, these diseases still remain a problem because a few cancerous cells avoid destruction and cause a relapse. This process is known as “self-renewal” and it leads to the reappearance of the disease with the possibility of metastasis.
The main author of the study, associate professor Catriona Jamieson, MD, reports that inflammation is responsible for boosting the activity of the ADAR1 (adenosine deaminase) enzyme. Her research team includes researchers from Italy, Canada and from the United States. According to Jamieson, this particular enzyme is expressed early in one’s life and plays a role in the development of blood cells. Afterwards, the enzyme deactivates and is only triggered back on by viral infections. However, the effect of the enzyime in leukemia is that its over-expression amplifies the splicing of RNA, thus leading to a more powerful “self-renewal” process. The current research projects aids precedent studies led by both Jamieson and other researchers. “People normally think about DNA instability in cancer, but in this case, it’s how the RNA is edited by enzymes that really matters in terms of cancer stem cell generation and resistance to conventional therapy.” The described RNA editing process, which occurs in the context of human and other primate specific sequences, also underscores the importance of addressing inflammation as “an essential driver of cancer relapse and therapeutic resistance”, notes Jamieson. She added that the discovery of the enzyme’s role creates the possibility of new future therapies. Jamieson suggests that a future therapy capable of blocking the stem cells in leukemia from using the ADAR1 enzyme could stop the cloning of malignant stem cells. Precedent studies have shown that CML is initiated by a chromosomal abnormality that causes the formation of a mutant gene called BCR-ABL on chromosome 22. CML is usually diagnosed in its late stages due to a dramatic increase of malignant cells. This sudden growth is known as a blast crisis. Most patients are diagnosed around the age of 65. There have been major improvements in CML treatment due to the discovery of tyrosine kinase inhibitor therapies. However, most of the patients will experience a relapse if the therapy is stopped due to the fact that there are several cancer stem cells that are resistant to this therapy.
The current study offers a novel therapy target that could be able to stop the relapse and progression of CML. Approximately 70 thousand people suffer from CML in the United States. This number is predicted to double by the year 2050. Despite the fact that researchers have discovered that the mutant BCR-ABL gene is responsible for the onset of the disease, the cause of the mutation has not yet been identified.