PRESS RELEASE
NEW FUNCTION OF ONE OF THE GENES MOST INVOLVED IN CANCER BRINGS FURTHER POSSIBILITIES TO LEUKAEMIA TREATMENT

• In the field of acute myeloid leukaemia researchers from the CRG have found a way to eliminate the carcinogenic activity of the Myc gene, present in the majority of cancers, while at the same time boosting its hitherto unknown anticancer activity

• The new anti-tumour activity of Myc boosts the maturity of the leukaemic cells, aiding the retinoic acid, the therapeutic agent of choice in the treatment of actute promyelocytic leukaemia.

• The study was published on October 23rd in the journal Nature Cell Biology

The Epigenetic Events in Cancer research group from the Centre for Genomic Regulation (CRG) has carried out a study which explains how to change the activity of the “Myc gene” in the development of cancerous tumours. The work forms part of the doctoral thesis of Dr. Iris Uribesalgo, supervised by Luciano Di Croce, researcher from the ICREA, and with the collaboration of the Epithelial Homeostasis and Cancer group, directed by Salvador Aznar-Benitah, also at the CRG.

All of the cells in our body are different. They all originate from stem cells and, as these divide, the new cells differentiate into distinct cell types, e.g., muscle, blood and cardiac cells. First, the stem cells “proliferate” (they divide) and then they “differentiate” (they change into cells with specific functions). When a cell continues to proliferate without differentiating, it becomes a tumour cell. For this reason, the researchers aim to keep the proliferation at normal levels and for each cell to differentiate correctly.

Until now, Myc has been described as causing the appearance of multiple tumour types, always associated with the protein “Max”. The researchers have discovered that if Myc and Max are separated, cell proliferation is halted and, additionally, the Myc gene goes on to stimulate the activity of a well-known differentiating agent, the Retinoic Acid Receptor (RAR), together with which it achieves the differentiation of the tumour cells making them once again functional. "For the first time we have found that Myc can change its function, from being responsible for a normal cell becoming cancerous, it converts into a tumour suppressor," says Luciano Di Croce, director of the research at the CRG.

In the case of promyelocytic leukaemia this discovery is key, as the most common treatment is a cocktail of the drug Retinoic Acid, which stimulates differentiation, and “Ara-C” chemotherapy. The researchers have discovered that “Ara-C” acts by changing the function of Myc. The main author of the study, Iris Uribesalgo, says, “These results can help in the understanding of how to control the two drugs which are normally used to combat this kind of leukaemia”. The findings do not mean new clinical treatment for patients with this cancer, but rather possibilities for the creation of more effective therapies in order to reduce side effects.

The study was done, in part, using cells from patients at the Hospital de la Santa Creu i Sant Pau in Barcelona, and thanks to funding from the Spanish Ministries of Health and Science and Innovation, AGAUR and the Fundació La Marató.

Reference work: Uribesalgo I, Buschbeck M, Gutiérrez A, Teichmann S, Demajo S, Kuebler B, Nomdedéu JF, Martín-Caballero J, Roma G, Benitah SA, Di Croce L. E-box independent regulation of transcription and differentiation by c-Myc. Nat. Cell Biol. DOI: 10.1038/ncb2355

Note for journalists:

For further information: Juan Sarasua, Press Office, Communication and Public Relations Dept., Centre for Genomic Regulation (CRG). Tel. +34 93 316 02 37 - juan.sarasua@crg.eu

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