In a recent study, published in Nature Communications on April 30, 2021, scientists learned that a specific genetic mutation, which has long been linked to a poor prognosis in certain blood cancers, plays a key role in the development of cancers when combined with other mutations, which was observed in both mice and human cells. The study helped scientists understand how a certain mutation in the gene known as a cut-like homeobox 1 (CUX1), aids in the development of acute myeloid leukemia, which is a type of cancer that forms in the blood and bone marrow.
Commonly referred to as AML, acute myeloid leukemia is a rapidly progressing blood cancer that affects a group of white blood cells known as a myeloid; which eventually will go on to become mature blood cells such as red blood cells and platelets. This type of leukemia occurs as a result of a mutation within the bone marrow cells. As a result, AML will typically develop first in the bone marrow, where it can grow and eventually ‘crowd out’ otherwise healthy blood cells, leading to life-threatening infections and bleeding.
To date, there has been little understanding as to what causes the mutations in a person’s bone marrow that leads to the development of AML. In previous studies conducted by the Wellcome Sanger Institute, scientists found that “loss-of-function mutations in the CUX1 gene on chromosome 7q were seen in several types of cancer, including AML, where it is associated with poor prognosis.”
In their new study, the scientists used a type of technology called CRISPR/Cas9 gene-editing—a process in which gene sequences are transcribed into short RNA sequences that are capable of guiding the system to matching sequences of DNA—to show that a shortage of working CUX1 increased the development of a gene known as CFLAR.
CFLAR is a gene that encodes a type of protein that halts the process of apoptosis, the programmed death of cells that occurs in multicellular organisms. This could mean that certain cancerous cells may be able to evade cell death and spread in cases where the CUX1 genes are not working.
Scientists used this newfound knowledge to try and observe this relationship between genes. They found that by targeting CFLAR, a potentially new type of treatment for people with AML could be developed, especially for those with a poor prognosis. While there are currently no clinically approved drugs that target CFLAR, scientists believe that focusing future treatments on these specific genes could be the answer for developing future ones.
Dr.Chi Wong, senior author of the study and Clinical Fellow at the Wellcome Sanger Institute and Honorary Consultant Haematologist at Addenbrooke’s Hospital said,
“Acute myeloid leukemia is a devastating disease, which is currently difficult to treat, especially in cases characterized by genetic lesions such as loss of CUX1 and chromosome 7q deletions. This new study provides evidence that could be used to help develop new targeted treatment for some people living with acute myeloid leukemia, offering hope for this group of patients who unfortunately are more likely to have a poor prognosis.”