Genes May Explain Leukemia Treatment Failures
Findings Could Lead to Better Treatment for Patients
Aug. 4, 2004 -- A relatively small number of genes may
determine whether leukemia treatment succeeds or fails, according to a new
Researchers in the U.S. and the Netherlands found the newly
identified set of genes were linked to either resistance or sensitivity to the
four cancer drugs commonly used to treat acute lymphobastic leukemia (ALL).
The results may help explain why, despite major recent advances
in treatment, nearly 20% of children with leukemia still do not respond to
"We've known for years that certain genetic changes in
leukemic cells are associated with a high risk of treatment failure," says
researcher William Evans, PharmD, scientific director of St. Jude Children's
Research Hospital in Memphis, Tenn., in a news release. "The findings of
this study are helping us understand why patients respond differently to
treatment and point to new approaches to overcome these causes of disease
The findings appear in the Aug. 5 issue of the New England
Journal of Medicine.
Genes Linked to Drug Resistance
In the study, researchers tested leukemia cells from 173 Dutch
children newly diagnosed with leukemia for sensitivity to four common
chemotherapy drugs used in leukemia treatment.
Researchers found a particular group of genes that when present
in leukemia cells determined their sensitivity or resistance to the four
chemotherapy drugs. Of the 124 genes identified, 121 had not been previously
associated with resistance to the four chemotherapy drugs tested.
The study also showed that these genes predicted treatment
success or relapse in both the 173 Dutch children as well as another group of
98 children with leukemia who were treated with the same drugs at St. Jude.
"The gene expression patterns linked to drug resistance
were particularly important since they occurred in both the Rotterdam and the
St. Jude patient populations, even though these two groups of children were
treated with these drugs in different countries and on different
protocols," says Rob Pieters, MD, chair of pediatric oncology/hematology at
Erasmus University in Rotterdam, the Netherlands, in the release. "This is
strong evidence of the link between these resistance genes and treatment
Findings Will Lead to Better Treatment
In an editorial that accompanies the study, Naomi J. Winick,
MD, of the University of Texas Southwestern Medical Center in Dallas, and
colleagues say that these findings will lead to new, more targeted treatments
"The gene-expression patterns these authors describe can be
used to begin to define the mechanisms of resistance and will stimulate the
development of alternative treatment strategies, targeted to those with
resistant disease identified at diagnosis," write the editorialists.
They say the identification of a gene profile that predicts the
outcome of treatment would also allow treatment to be personalized early on and
avoid use of unnecessary and ineffective drugs.