Long non-coding RNAs

Dr Jennifer Lynch, 2014 Balnaves Young Researcher of the Year, is using her $100,000 award to support a one-year research project aimed at better understand long non-coding RNAs in acute childhood leukaemia.

An early-career researcher with the Cancer and Stem Cell Biology Group at Children’s Cancer Institute Australia (CCIA), Lynch will look at whether targeting long non-coding RNAs can provide a potential new way of treating acute lymphoblastic leukaemia (ALL).

“I recently recruited a research assistant,” said Lynch, who is in the second year of her postdoc at CCIA. “So the work has just started. We plan to look at a particularly aggressive subtype of ALL, called MLL-rearranged ALL.”

ALL is an acute form of leukaemia characterised by the overproduction of lymphoblasts - cancerous immature white blood cells. The lymphoblasts accumulate in the bone marrow and impede the production of normal blood cells.

ALL is most common in children between 2 and 5 years of age.

MLL-rearranged ALL is the most aggressive subtype of childhood leukaemia and has a very poor prognosis. It is characterised by a high incidence of chromosomal translocations or rearrangements in the MLL gene. These chromosomal rearrangements are an important predictor of adverse outcome.

“We aim to begin figuring out how this chromosomal rearrangement contributes to the aggressiveness of MLL-rearranged leukaemia,” explained Lynch. “Several long non-coding RNAs have been characterised and linked to the MLL-rearrangement and we plan to look at how they contribute to the disease and to maintenance of the disease.”

Long non-coding RNAs are part of a large set of non-protein coding transcripts that, combined with short non-coding RNAs and the protein-coding messenger RNAs, form the human transcriptome.

Not a lot is known about the function of long non-coding RNAs, but they have been linked to blood development and cancer.

Lynch will use recently reported evidence on the association of long non-coding RNAs with ALL as well as investigating a novel long non-coding RNA her group at CCIA believe to be associated with acute myeloid leukaemia (AML).

“We have a publication in the pipeline on a gene that we propose plays a critical role in regulating stem cell behaviour in AML and we have evidence to suggest that this gene might be regulated by a long non-coding RNA,” Lynch said.

Lynch said long non-coding RNAs are also known to interact with chromatin-modifying complexes and regulate gene expression. She plans to look at the different expression of specific genes between wild-type leukaemia and MLL leukaemia as well as identify binding partners that interact with the long non-coding RNAs.

“We know that the activity of long non-coding RNAs depends on their physical interaction with binding partners,” Lynch said. “Identifying critical binding partners provides the opportunity to develop inhibitors that perturb the interaction of long non-coding RNAs with binding partners and potentially develop a new way of treating ALL.

“Understanding the mechanisms of action of these molecules and how they contribute to cancer will facilitate the development of more targeted therapies.”

Dr Denise Yu, a research officer with the Experimental Therapeutics Program at CCIA, also received a $100,000 award for her research to identify metabolic pathways in cancer cells that may be new targets for treating neuroblastoma - the most common solid cancer found in infants.

The Balnaves Foundation established the Balnaves Foundation Young Researcher’s Fund in 2008 to support the development of original ideas in childhood cancer research. Through the foundation, renowned Australian philanthropist Neil Balnaves AO invests more than $2.5 million each year to support education, medicine and the arts with a focus on young people, the disadvantaged and Indigenous communities