New drug target for leukemia identified

A new drug target for treating leukemia has been identified as part of the largest ever genetic analysis of tumor growth in childhood blood cancer.

By blocking the action of an RNA strand present only inleukemia patients, the researchers were able to slow the cancer's progression.

T-cell acute lymphoblastic leukemia is one of the most common and aggressive childhood blood cancers. Every year, an estimated 500 American adolescents with this blood cancer fail to achieve remission through standard chemotherapy.

Using genetic scanning techniques, researchers at NYU Langone Medical Center identified 6,023 long, non-coding strands of RNA active in immune system T cells taken from a group of T-cell acute lymphoblastic leukemia patients.

These strands of RNA from the 15 patients were not active in the healthy T cells of three young people who did not have leukemia.

Publishing their findings in the journal Cell, the researchers describe how they were able to block the action of one of these RNA strands - leukemia-induced non-coding activator RNA-1 or "LUNAR1" - which had the effect of slowing leukemia progression.

Long-coding sequences of RNA, such as LUNAR1, are increasingly recognized as being important in regulating cell functions, say the scientists. Previously, they were thought of as "junk DNA," which help to transcribe DNA without fully assembling proteins.

Although LUNAR1 does not produce cancerous proteins itself, it forms an important part of the signaling action of a protein related to many cancers - insulin-like growth factor 1receptor (IGF-1R).

NOTCH1 pathway active in leukemia patients led to discovery of LUNAR1

The researchers found LUNAR1 by examining RNAs active in a biological pathway known as NOTCH1. This pathway is active in at least half of all T-cell acute lymphoblastic leukemia patients, and the researchers found that LUNAR1 was the most highly expressed long, non-coding RNA associated with NOTCH1.

In normal T cells, explain the authors, NOTCH1 is inactive, and LUNAR1 and other long, non-coding RNAs are not transcribed and can not bind to and activate IGF-1R.

The researchers found that LUNAR1 was overproduced in 90% of the leukemia patients in the study. Drugs blocking LUNAR1 could therefore form the basis of an alternative treatment to chemotherapy, which kills healthy cells as well as cancer cells.

The team transplanted human leukemia T cells into mice and then successfully stalled tumor growth in a subset of the mice by chemically blocking LUNAR1.

The study shows that LUNAR1 is highly specific for T-cell acute lymphoblastic leukemia and plays a key role in how this cancer develops.

To test this, the research team transplanted human leukemia T cells into mice and then successfully stalled tumor growth in a subset of the mice by chemically blocking LUNAR1.

The research suggests that future therapies for cancer should take into account the RNA make-up of individual patients, as well mutations in their DNA.

The next step for the team is to develop drugs that can more effectively inhibit LUNAR1, perhaps by targeting its component nucleotides.

In 2013, researchers reported on a study that used modified T cells to induce remission in five adult patients with acute lymphoblastic leukemia.

Earlier this year, researchers also investigated how a fusion gene that "rearranges" the DNA of cancer genesmay contribute to the development of acute lymphoblastic leukemia. The researchers behind that study hope their findings will open doors for further leukemia treatments.