Turning Cancer Cells Into Normal Cells

Illustration of Cancer Cells

Cancer of the body’s blood-forming tissues, such as the lymphatic system and bone marrow, is known as leukemia.

A mechanism is discovered that explains how cancer cells transform into normal, harmless ones.

A recent study explains how changing the chemical modifications, or so-called epigenetics, of a specific type of leukemia cell’s genetic material, the messenger RNA, leads to the transformation of highly proliferative leukemia cells into normal cells that no longer multiply.

The study, which was published in the journal Leukemia, is authored by Alberto Bueno-Costa, a researcher in the group of Dr. Manel Esteller, supervisor of the research and Director of the Josep Carreras Leukaemia Research Institute, ICREA Researcher and Professor at the University of Barcelona.

Cancer is a condition in which a healthy cell changes into a malignant one with entirely new traits, such as the ability to divide uncontrollably. Numerous molecular alterations that cause this transformation of healthy tissue into tumor tissue have been identified via extensive research in recent years. However, nothing is known about the opposite process, which involves changing a cancer cell into a normal, non-cancerous one, and the variables that may be involved in this process.

Alberto Bueno Costa and Manel Esteller

First author, Alberto Bueno-Costa, and chief supervisor, Dr. Manel Esteller. Credit: Josep Carreras Leukaemia Research Institute

“We know that one strategy that human tumors have to dodge the effectiveness of drugs is to change their appearance, becoming another similar cancer but insensitive to the drug used. For example, leukemias of the lymphoid lineage are switched to the myeloid strain to escape treatment”, explains Dr. Esteller. With this idea in mind, they wanted to know more about the molecular pathways involved in these cellular metamorphoses and studied an in vitro model where leukemia cells can be forced to turn into a type of harmless immune cells called macrophages.

Experimental results showed that the reversal of the malignant cells into macrophages involved a profound change in the chemical changes occurring on their messenger RNAs, the carriers that help proteins formation. In particular, the changes affected the distribution of an epigenetic mark called methylated adenine.

This change in the chemical accentuation of these molecules causes instability of the proteins that define leukemia while favoring the appearance of differentiated proteins characteristic of the normal cell that is being born, the macrophage. This process appears to be controlled by the METTL3 gene, a manufacturer of chemical modifications targeting messenger RNA.

This line of research, though still in the preclinical stage, looks quite promising and is worth further exploring as a new approach in the fight against leukemia. In fact, as Dr. Esteller points out, “the first preclinical drugs against this target have already been developed in experimental models of malignant blood diseases, so we provide another reason why these novel drugs could be useful in cancer therapies, particularly in the case of leukemias and lymphomas.”

The more strategies being developed, the better for the thousands of patients diagnosed every year of blood malignancies. Perhaps, in the mid-term, turning leukemia cells into harmless types will be part of our arsenal against cancer.

Reference: “Remodeling of the m6A RNA landscape in the conversion of acute lymphoblastic leukemia cells to macrophages” by Alberto Bueno-Costa, David Piñeyro, Carlos A. García-Prieto, Vanessa Ortiz-Barahona, Laura Martinez-Verbo, Natalie A. Webster, Byron Andrews, Nitzan Kol, Chen Avrahami, Sharon Moshitch-Moshkovitz, Gideon Rechavi, and Manel Esteller, 9 June 2022, Leukemia.
DOI: 10.1038/s41375-022-01621-1

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