Just like the fabled Ikaros who met his demise when he flew too close to the sun, a gene of the same name may spell trouble for cancer patients. A new study indicates that mutations in the Ikaros gene play a role in triggering acute lymphoblastic leukemia (ALL), an aggressive, treatment-resistant form of cancer. Researchers hope the find will lead to new ways to tackle the disease.
A chromosomal rearrangement called the Philadelphia chromosome causes chronic myelogenous leukemia (CML), a cancer of blood cells that patients can live with for years and generally recover from with treatment. But the same defect is also found in a small percentage of patients with ALL, which can be fatal in months and is difficult to treat. Researchers have long wondered what differentiates the two diseases. One possible culprit is Ikaros. Children with mutations in the gene, but who don't have the Philadelphia chromosome, develop ALL.
To find out if Ikaros also plays a role in Philadelphia chromosome-associated ALL, a team led by James Downing, a hematopathologist at St. Jude Children's Research Hospital in Memphis, Tennessee, looked at ALL patients who also had the Philadelphia chromosome, including 21 children and 22 adults. The majority of the patients had a flawed copy of the gene, with mutations occurring in 76.2% of the children and 90.9% of the adults, the researchers report this week in Nature. The Ikaros mutations were not found in 23 adults with CML, confirming the role of this gene in triggering ALL in those with the Philadelphia chromosome. Ikaros codes for a transcription factor protein that is essential for normal development of white blood cells called lymphocytes, but it is not yet clear how the mutations lead to cancer. One possibility is that the faulty protein produced by the mutations leads to abnormal lymphocytes that turn cancerous, Downing says.
Mitchell Smith, an oncologist at Fox Chase Cancer Center in Philadelphia, Pennsylvania, says the finding is "a big advance" that could pave the way for treatments. "There's nothing available today that will fix this, but once you know what you're after, it becomes easier to target," he adds. William Phelps, a molecular biologist at the American Cancer Society in Atlanta, Georgia, says the Ikaros protein itself probably won't make a good target for drugs because it's a transcription factor, and such proteins don't have binding sites to which compounds that block their action can adhere. But other genes or proteins that Ikaros regulates may make good targets for drugs, he adds.