New Therapy to Halt Lethal Childhood Leukemia

by Dr. Meenakshy Varier on  January 7, 2017 at 2:25 PM Health Watch
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Highlights
  • Mixed lineage leukemia (MLL) is an aggressive form of leukemia that primarily strikes newborns and infants.
  • It is caused by an errant chromosome 11 on MLL gene, which has two versions- chimeric and wild type.
  • The MLL caused by the wild-type version had extremely low levels of a protein.
  • The newly identified compound helps stabilize MLL protein that impedes MLL leukemia cell growth and halts its progress
The genetic driver of a rare and lethal childhood leukemia called as mixed lineage leukemia has been identified along with a targeted molecular therapy that halts the proliferation of leukemic cells.
New Therapy to Halt Lethal Childhood Leukemia
New Therapy to Halt Lethal Childhood Leukemia

The finding by scientists from the Northwestern University also has implications for treating other types of cancer.

"We've spent the last 20 years in my laboratory trying to molecularly understand how MLL translocations cause this rare and devastating form of leukemia in children so that we can use this information to develop an effective therapy for this cancer," said lead investigator Ali Shilatifard. "Now we've made a fundamentally important breakthrough."

Mixed Lineage Leukemia

Mixed lineage leukemia (MLL) is an aggressive form of leukemia that primarily strikes newborns and infants. Annually, 300 cases are seen across the U.S.

Mixed lineage leukemia is caused when an errant chromosome 11 on the MLL gene breaks and attaches to other chromosomes such as chromosome 19.

This mutation produces a protein that drives the pathogenesis of leukemia.

The prognosis of MLL is extremely poor. About 10% to 20% of those children do not live more than five years after being diagnosed.

Current Focus

Most research related to this cancer has focused on the errant version of chromosome 11. But there are two copies of chromosome 11- chimeric and wild-type.

The researchers investigated the wild-type version and discovered that in pediatric leukemia produced by the wild-type MLL gene, individual cells had extremely low levels of a protein.

The researchers then suggested increasing the levels of the wild-type MLL protein, so that it would help displace the mutated version that drives cancer. This could lead to a cure for MLL.

They then identified a compound that stabilized the wild-type MLL and interfered with the MLL leukemia cell proliferation.

To test its effectiveness of the new compound, researchers grew mixed lineage leukemia cells in a culture and transplanted them into mice.

They injected the therapeutic compound into the mice and found that the wild-type MLL returned to healthy levels, and the leukemic cells were not able to grow as rapidly.

Conclusion

Better compounds are now being synthesized and researchers hope to launch a Phase I trial to test these compounds in Chicago.

Researchers are hopeful about this breakthrough and are in the process of pushing their findings into clinic for the treatment of childhood leukemia.

The paper is published in the journal Cell.

Reference

  1. Ali Shilatifard et al. Therapeutic Targeting of MLL Degradation Pathways in MLL-Rearranged Leukemia. Cell; (2017) doi.org/10.1016/j.cell.2016.12.011


Source: Medindia

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