Novel drug shows promise for MLL leukemia

By Dr. Ananya Mandal, MDOct 3 2011

According to British scientists a potential new drug from GlaxoSmithKline could treat mixed-lineage leukemia (MLL). MLL is the most common form of leukemia in babies. The study appeared in the journal Nature where scientists from the British drugmaker collaborating with the charity Cancer Research UK (CRUK) and Cellzome AG found that the experimental drug, called I-BET151.

The new drug mimics a chemical tag which is important in preventing the process of activating the leukemia genes. Tony Kouzarides of the Wellcome Trust/CRUK Gurdon Institute at Cambridge University, who co-led the study said, “This ... is an exciting new avenue for drug discovery which we hope will be useful for other types of cancer in addition to MLL-leukaemias.” Kevin Lee, head of epigenetics discovery research at GSK, who also worked on the study, said he too was excited about the findings, although it will probably be many years before the drug could potentially reach the market. He added, “Even though this is still lab-based ... it validates the idea of developing small molecules against epigenetic switches… It is important to remember we will need to be successful on a number of additional steps before we can move this from the lab to testing this compound in humans.”

MLL leukemia is thought to account for up to 80 percent of cases of acute leukemia in children below two years old, and up to one in 10 cases in adults. Most patients don't respond well to standard leukemia treatments and often the cancer comes back. Researchers explain that in MLL gene called MLL gets fused to another gene. This disrupts the normal function of MLL by creating a new “fusion protein” that behaves wrongly, switching on genes that drive the development of leukemia.

Kouzarides's team found that in the disease, the MLL-fusion proteins are targeted to leukemia-causing genes by proteins from the BET family which recognizes certain chemical “tags” on chromatin, the scaffold on which DNA is arranged. The team used I-BET151 to treat leukemia in mice and human cancer cells in a lab. They noted that the chemical could halt the disease, paving the way for more research to be done in first-stage, or so-called Phase I, human trials.

“We urgently need better ways to treat children with more aggressive forms of leukemia, such as MLL…Although this research is only in the lab at the moment, we hope it will move quickly toward clinical trials in patients,” said Lesley Walker, CRUK's director of information.