[OT] Mutation May Explain Deadly Form of Leukemia

April 19, 2008

Mutation May Explain Deadly Form of Leukemia

By Steve

ScienceNOW Daily News

14 April 2008

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 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.

, 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. 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.

Recommended Posts