Scientists Identified Potential New Drug Target for Leukemia Treatment
A new drug target for the treatment of leukemia has been discovered as part of the biggest ever genetic evaluation of tumor development in childhood blood cancer.
T-cell acute lymphoblastic leukemia is among the very common and aggressive childhood blood cancers. Each year, around 500 American teenagers with this type of blood cancer fail to obtain remission through standard chemotherapy.
Applying genetic scanning methods, scientists at NYU Langone Medical Center recognized around 6,000 long, non coding strands of RNA active in immune system T cells obtained from a group of T-cell acute lymphoblastic leukemia sufferers.
These strands of RNA from the 15 sufferers were not active in the healthy T cells of 3 young individuals who did not have leukemia.
Presenting their results in the journal Cell, the scientists explain how they were capable to prevent the action of one of these RNA strands – leukemia-stimulated non-coding activator RNA-1 or “LUNAR1” – which had the effect of reducing leukemia development.
Long-coding series of RNA, like as LUNAR1, are progressively identified as being significant in controlling cell functions, say the researchers. Formerly, they were considered of as “junk DNA,” which assists to transcribe DNA without completely assembling proteins.
Even though LUNAR1 does not generate cancerous proteins by itself, it forms an essential part of the signaling action of a protein associated to many cancers – insulin like growth factor 1receptor (IGF-1R).
NOTCH1 pathway active in leukemia sufferers lead to development of LUNAR1
The scientists found LUNAR1 by analyzing RNAs active in a biological process identified as NOTCH1. This process is active in a minimum of half of all T-cell acute lymphoblastic leukemia sufferers, and the scientists identified that LUNAR1 was the most extremely expressed long, non-coding RNA connected with NOTCH1.
In regular T cells, describe the authors, NOTCH1 is inactive, and LUNAR1 and other long, non-coding RNAs are not transcribed and can’t join to and activate IGF-1R.
The scientists identified that LUNAR1 was over-produced in 90% of the leukemia sufferers in the research. Drugs preventing LUNAR1 could consequently form the foundation of an alternative therapy to chemotherapy, which destroys healthy cells along with cancer cells.
Our research indicates that LUNAR1 is extremely specific for T-cell acute lymphoblastic leukemia and performs a key part in how this cancer develops,” states Iannis Aifantis, PhD, a professor and chair of pathology.
To examine this, Dr. Aifantis and group transplanted human leukemia T cells into mice and then efficiently delayed tumor growth in a subset of the mice by chemically preventing LUNAR1.
The research recommends that upcoming therapies for cancer must take into account the RNA make-up of individual sufferers, also mutations in their DNA.
The next move for the group is to develop medicines that can more successfully inhibit LUNAR1, probably by targeting its component nucleotides.
Earlier this year, scientists also examined how a fusion gene that “re-arranges” the DNA of cancer genes may play a role to the progression of acute lymphoblastic leukemia. The scientists behind that research hope their discoveries will open doors for additional leukemia treatments.