New ‘poison’ discovery could pave way for leukaemia therapyDecember 4th, 2010 - 12:47 pm ICT by ANI
Washington, Dec 4 (ANI): Research led by Weill Cornell Medical College revealed that newly identified mutant enzymes in AML create a chemical poison to cause leukaemia.
The findings should prove useful in treating patients by providing a molecular target against which to develop new drugs against one subset of AML as well as other cancers.
People with AML have abnormal cells inside their bone marrow that quickly multiply, replacing healthy blood cells in the bone marrow and leading to infections, bleeding and severe anaemia.
Using computational tools to sift through millions of data points, the team discovered a unique chemical signature in the genomes of patients with mutations in either of two enzymes called IDH1 and IDH2, which occur frequently in AML.
Dr. Ari Melnick, Dr. Craig B. Thompson, Dr. Ross L. Levine and their team members discovered that this chemical signature: a massive accumulation of DNA methylation that causes genes to function abnormally, leading to AML.
They went on to show that IDH1 and IDH2 mutations generate a “poison” that blocks the ability of a protective factor called TET2 to remove the methylation from the genome.
They also showed that many AML patients have mutations that inactivate TET2, and this causes the same abnormal DNA methylation effect as IDH1 and IDH2 mutations.
“One of the great surprises of this study was that IDH1 and IDH2, which are normally involved in energy metabolism and located far away from DNA and outside of the cell nucleus, could become subverted to make a substance that poisons the genome,” said Melnick.
“Our study shows for the first time that metabolic enzymes not only help to fuel tumour growth but when mutated can also directly ‘rewrite’ the instructions that govern the genome,” he added.
One important implication of this work is that it appears technically feasible to create drugs that can specifically stop mutant IDH1 and IDH2 from making the cancer-causing poison.
Such inhibitors have the potential to fundamentally restore normal functioning to the genome and thus help to treat leukaemias.
The study is published today in the online edition of the journal Cancer Cell. (ANI)
- Gene mutation 'key to glioma brain cancer growth' - Nov 23, 2009
- Fish oil may hold key to leukaemia cure - Dec 23, 2011
- Compound to starve cancers of sugar-based building blocks found - Nov 19, 2010
- 'Chewing betel leaf may help fight cancer' - Sep 18, 2012
- Turning diseased blood cells to stem cells may reveal cancer quickly - Feb 05, 2011
- Boffins discover key enzyme in DNA repair pathway - Jul 30, 2010
- Gene mutation behind onset of acute myeloid leukaemia identified - Mar 28, 2011
- 'Body's natural cell-suicide program can fuel tumour development' - Aug 01, 2010
- Mouse genome offers human cancer clue - Mar 24, 2011
- Scientists complete whole-exome sequencing of skin cancer - Apr 16, 2011
- Gene causing lung cancer identified - Jan 07, 2012
- How loss of key protein promotes aggressive form of leukaemia - Jul 02, 2010
- Mechanism that could provide potential cure for diabetes identified - Apr 30, 2011
- DNA test to detect early bowel cancer could be 1 step closer - Mar 05, 2011
- Personalized cancer medicine now a step closer to reality - Apr 16, 2011
Tags: abnormal cells, aml patients, blood cells, cell nucleus, chemical signature, computational tools, cornell medical college, dna methylation, dr ross, energy metabolism, massive accumulation, melnick, metabolic enzymes, molecular target, mutant enzymes, new drugs, new poison, thompson dr, weill cornell medical, weill cornell medical college