Turning Cancer Cells Into Normal Cells



There is now a method that explains how cancer cells become innocuous, normal cells.

According to a new study, altering the chemical alterations, or so-called epigenetics, of a particular type of leukemia cell's genetic material, the messenger RNA, causes the leukemia cells to change from highly proliferative to normal cells that stop growing.

Alberto Bueno-Costa, a researcher in the lab of Dr. Manel Esteller, director of the Josep Carreras Leukaemia Research Institute, ICREA researcher, and professor at the University of Barcelona, is the study's lead author. The work was published in the journal Leukemia.

When a healthy cell develops cancer, it transforms into a malignant one with wholly new characteristics, such the capacity to divide uncontrollably. The transformation of healthy tissue into tumor tissue is triggered by a variety of molecular changes, which have been extensively studied in recent years. The reverse process, which transforms a cancer cell into a normal, non-cancerous one, and the factors that can be involved in this process, are unknown.

Dr. Manel Esteller is the principal overseer and Alberto Bueno-Costa is the first author. Photograph courtesy of Josep Carreras Leukemia Research Institute

"We are aware that one tactic employed by human tumors to evade the effects of medications is to alter their appearance and transform into a different malignancy that is less susceptible to the medication being used. For instance, lymphoid lineage leukemias convert to the myeloid strain to evade treatment, according to Dr. Esteller. With this in mind, they investigated an in vitro model where leukemia cells may be made to transform into a kind of benign immune cells known as macrophages in order to learn more about the molecular processes involved in these cellular metamorphoses.

According to experimental findings, the transformation of malignant cells into macrophages involved a significant alteration in the chemical alterations taking place on their messenger RNAs, the carriers that assist in the production of proteins. The distribution of methylation adenine, an epigenetic marker, was particularly impacted by the modifications.

The proteins that distinguish leukemia become unstable as a result of this modification in the chemical accentuation of these molecules, supporting the development of differentiated proteins distinctive of the developing normal cell, the macrophage. The METTL3 gene, which produces chemical alterations directed at messenger RNA, appears to be in charge of this process.

Even though it is still in the preclinical stage, this line of study is highly promising and merits further investigation as a fresh strategy in the fight against leukemia. According to Dr. Esteller, "the first preclinical medications against this target have already been created in experimental models of malignant blood disorders, thus we present another reason why these innovative drugs could be effective in cancer therapy, notably in the case of leukemias and lymphomas."

The more treatment options that are developed, the better for the thousands of patients who are diagnosed with blood cancers each year. Perhaps in the medium run, converting leukemia cells into benign ones will be a tool in our cancer-fighting armory.

Ref: "Remodeling of the m6A RNA landscape in the conversion of acute lymphoblastic leukemia cells to macrophages," by Alberto Bueno-Costa, David Pieyro, Carlos A. Garca-Prieto, Vanessa Ortiz-Barahona, Laura Martinez-Verbo, Natalie A. Webster, Byron Andrews, Nitzan Kol, Chen Avrahami, Sharon Moshitch-Moshkov

By JOSEP CARRERAS LEUKAEMIA RESEARCH INSTITUTE  

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