Healthy cells become malignant cells in cancer, which have radically different properties, such as the propensity to divide uncontrollably.
Leukemia is a type of blood malignancies that start in the bone marrow and produce a significant number of abnormal blood cells due to a lack of normal blood cells. Bleeding and bruising, bone discomfort, weariness, fever, and a higher risk of infection are all possible symptoms.
While the actual aetiology is unknown, it is thought to be caused by a mix of genetic and environmental factors, including smoking, ionising radiation, exposure to certain chemicals such as benzene, chemotherapy, and Down syndrome.
Despite the fact that leukaemia is the most frequent malignancy in children, more than 90% of all leukemias are diagnosed in adults.
Wouldn’t it be amazing if highly proliferative leukaemia cells that grow and multiply quickly could be transformed into normal cells that don’t multiply? It’s like putting a jack-in-the-box back in its box.
This was accomplished thanks to new research led by scientists in Barcelona, Spain, with significant contributions from colleagues at Tel Aviv University’s Sackler Faculty of Medicine’s Department of Human Genetics and Biochemistry: Prof. Gideon Rehavi, Nitzan Kol, Chen Avrahami, and Sharon Moshitch-Moshkovitz. “Remodeling of the m6A RNA landscape in the conversion of acute lymphoblastic leukaemia cells to macrophages,” they published their findings in the high-impact journal Leukemia.
The article explains how leukaemia cells become normal cells that no longer reproduce by altering the chemical alterations – known as epigenetics – of messenger RNA, a form of genetic material. Alberto Bueno-Costa, a researcher with Dr. Manel Esteller’s group at the Josep Carreras Leukemia Research Institute at the University of Barcelona, was among the Spanish volunteers.
Following extensive research
Healthy cells become malignant cells in cancer, which have radically different properties, such as the propensity to divide uncontrollably. Various molecular modifications responsible for this switch from healthy to malignant tissue have been the subject of extensive research in recent decades. Scientists have known relatively little about the reverse process — converting a cancer cell into a normal, noncancerous one – and the components that might mediate this process until now.
“We know that one technique employed by human malignancies to avoid treatment effectiveness is to change their appearance, morphing into another tumour that is insensitive to the drug in question,” the researchers added. “Leukemias of the lymphoid lineage, for example, are converted to the myeloid strain to avoid treatment.”
They were interested in learning more about the chemical processes involved in this cellular change because of this idea. They looked at an in vitro model (an experiment done outside of a real organism, usually in a test tube or petri dish) in which leukaemia cells can be pushed to transform into macrophages, which are a type of innocuous immune cell.
The reversal of malignant cells into macrophages required a massive modification in the chemical alterations occurring on their messenger RNA – the carriers that enable proteins develop – according to experimental findings. The modifications had a particular impact on the distribution of methylation adenine, an epigenetic signature.
This shift in the angle established by two neighbouring chemical bonds in these molecules leads the proteins that identify leukaemia to become unstable, while favouring the production of microphages – proteins seen in newly generated normal cells.
Despite the fact that this line of study has yet to be tested on patients, the team believes it is promising and worthy of further investigation as a new way to fighting leukaemia. The more tactics found to combat leukaemia, the more hope there is for the half a million individuals diagnosed with blood cancers each year throughout the world.
Perhaps one day, changing leukaemia cells into non-cancerous types will be part of oncologists’ and haematologists’ cancer-fighting armament.
“Because the first preclinical drugs against this target have already been developed in experimental models of malignant blood diseases, we provide yet another reason why these novel drugs could be useful in cancer therapies, particularly in the case of leukemias and lymphomas,” says the study’s lead author.