Fetal origin could be infant leukemia’s “Achilles heel”

29 October 2021

CRM scientists have identified key genes, involved in both early fetal development and infant leukemia, which could be used as targets to treat this devastating disease.

The researchers, led by Professor Katrin Ottersbach, looked at which genes were switched on in fetal, newborn and adult stem cells from mice and humans and have found several genes in fetal cells which are critical to the survival of infant Leukaemia cells.

Acute lymphoblastic leukaemia is one of the most common cancers in children. The majority of patients respond well to existing treatments, however patients with a particular form of the disease MLL-AF4 acute leukaemia - have a very poor prognosis.

Scientists have little information about the molecular mechanisms responsible for the disease progression, which hinders the development of new treatments.

The team measured mRNA, the molecule that decodes DNA to produce the proteins that make up cells in both mouse and human cells. The profile of mRNAs present in a cell is called the transcriptome.

Professor Ottersbach, Dr Vasiliki Symeonidou and colleagues found that the fetal transcriptome was characterised by genes relating to cell multiplication and aiding leukemia cell growth. In contrast, the adult and newborn transcriptome showed a higher expression of leukemia suppressor genes and those involved in immune system processes. 

Two genes in particular piqued interest, PLK1, as there is a readily available inhibitor, and ELOVL1 (which codes for Elongation of very long chain fatty acids protein 1), which raises the possibility of altered fatty acid metabolism as a novel feature of infant Leukemia.

Professor Ottersbach said, “This work is exciting because by determining which aspects of the disease are residues of its fetal origin, we have identified new, potential disease vulnerabilities, which could be exploited to treat infant leukemia.”

This work is published in Cell Reports and was funded by CRUK and the Medical Research Council.

Article in Cell Reports https://doi.org/10.1016/j.celrep.2021.109900