In a study to be published in the April 1 issue of Blood, researchers used "gene expression analysis" to measure the degree of activity of thousands of genes in 33 patients who had recently been diagnosed with adult T cell acute lymphocytic leukemia (T-ALL), a disease caused by the overproduction of immune cells known as T lymphocytes.
"The present study investigates, for the first time, the identification of gene expression profiles associated with both short-term and long-term outcome in adult patients with T-ALL," says Jerome Ritz, MD, of Dana-Farber, who served as senior author of the study with Robin Foa, MD, of the University "La Sapienza." "While approximately 70 percent of pediatric patients with T-ALL have excellent long-term response to intensive chemotherapy, adult patients have a much less favorable outcome. Previously, this poor prognosis of adult T-ALL patients had not been attributed to specific genetic events."
Sabina Chiaretti, MD, a research fellow at Dana-Farber, is the paper's first author.
Using microarray technology, investigators compared gene activity levels in patients who improved with chemotherapy to those who did not. The researchers identified a single gene, IL-8, that was unusually active – or "highly expressed" – in T-ALL cells from patients whose condition was resistant to chemotherapy.
They also found a group of 30 genes that were highly expressed in leukemic cells from patients who had complete remissions of the disease. By measuring the expression levels of three of those genes – AHNAK, TTK, and CD2 – researchers were able to correctly predict the duration of remission in 71 percent of the cases. Using the genes' activity to determine remission length also proved successful in T-ALL samples taken from a separate group of 18 patients.
Two conventional methods of predicting patients' outcomes – measuring the white blood cell count and comparing the similarities between normal and cancerous cells – were also evaluated and appeared to be less accurate than the three-gene expression approach.
The study's findings may help doctors adjust treatments based on patients' individual gene-expression profile, says Ritz, who is also a professor of medicine at Harvard Medical School. Further study of these genes may also lead to therapies that target specific genetic abnormalities in adult T-ALL patients.
Other authors of the paper include Xiaochun Li, PhD, and Robert Gentleman, PhD, of Dana-Farber, and Antonella Vitale, MD, Marco Vignetti, MD, and Franco Mandelli, MD, of the University "La Sapienza."
The research was funded by the National Institutes of Health and grants from the Leukemia and Lymphoma Society, the Ted and Eileen Pasquarello Research Fund, the Associazione Italiana per la Ricerca sul Cancro, the Instituto Superiore di Sanita, the Ministero dell 'Universita' e della Ricerca Scientifica, the Progetto FIRB, and the Associazone per le Leucemie Acute dell'adulto "Cristina Bassi" e Fondazione Cassa di Risparmio di Genova e Imperia.
Dana-Farber Cancer Institute (www.danafarber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Journal
Blood