University of New Mexico Health Sciences Center
| By Rachel Miller, HSC School of Medicine |
Some cancer researchers study the disease process at the cellular level in a laboratory. Others observe the disease process as it takes place in a patient. A team at UNM is combining these approaches in one study on T-cell acute lymphoblastic leukemia, or T-ALL, which predominantly affects adolescents and young adults.
Stuart S. Winter, MD, works on the clinical side, and is the chair of an international T-ALL study that will start late this year. This clinical trial will be the largest of its kind ever done in either adult or pediatric oncology. Winter is an associate professor in the UNM Department of Pediatrics' Division of Pediatric Hematology and Oncology.
On the bench side of the study is Richard Larson, MD, PhD, who will analyze the samples from this trial using gene microarray analysis. Larson is an associate professor in the UNM Department of Pathology and the school's senior associate dean for research.
The six-year study is sponsored by the Children's Oncology Group – a group of more than 250 institutions in the United States, Canada, Switzerland and New Zealand. It will involve approximately 1,100 children in the United States alone. Winter will oversee the clinical side of the study at all sites, and bone marrow samples collected from patients in the study will be sent to UNM for microarray analysis in Larson's lab. Together, Winter and Larson will analyze these samples in the context of important treatment end points that are being studied in the trial. The goal of this analysis will be to create a genetic profile to find genetic similarities among these leukemias, and to find markers that signal leukemia cells' ability to either grow or die under a variety of experimental conditions.
The clinical trial, which began in late 2005, is only the latest collaboration between Winter and Larson; they have been studying T-ALL together for eight years. Winter has always had an interest in basic science research. “I became interested in T-cells because, and this is totally biased, but because they're so important,” he said. “T-cells orchestrate all immune responses in the body.”
Larson's research focus has been in cell-to-cell adhesion, and Winter believed that some of Larson's findings could be used to help explain how leukemia cells grow in bone marrow. In 1997 he approached Larson about working together to answer the questions he had about the importance of adhesive ligands, particularly the LFA-1/ICAM-1 dyad in the survival of leukemia cells. “In 1997 I approached Richard and asked, ‘wouldn't it be fun to work together?' This eight-year partnership grew out of that 90-second conversation,” Winter said.
The major focus of pediatric leukemia research in the past few years has been to discover factors in the microenvironment of bone marrow that help leukemia cells survive, and to study the effects of chemotherapy on those cells. Specifically, researchers want to understand why some leukemia cells survive and grow after chemotherapy treatment. These few residual cells can lead to a relapse months or years later. “Leukemia cell survival is an important concept,” Larson said. The goal is to kill all leukemia cells. Winter said, “When leukemia cells die, the patient lives.”
This cytogenetic-based study has lead to great advances in the treatment of precursor B cell leukemias. However, cytogenetics does not seem to be as biologically important in T-ALL. Drs. Larson and Winter are looking instead at how genes are expressed in leukemia cells to find out if this genetic expression may hold the key to survival and regeneration.
Larson studies this gene expression using microarray analysis, which is able to analyze all 54,000 genes from a patient sample on a chip the size of a thumbnail. Independently funded by the National Cancer Institute, he will use this data to compare the genetic expression of leukemia cells from different patients over the next five years. He hopes that this comparison will help identify new diagnostic and prognostic markers in the genes. Currently, such markers do not exist.
Good prognostic markers would allow oncologists to customize chemotherapy treatments, so that patients whose genes show potential for a good outcome would receive less chemotherapy and therefore have fewer side effects. Patients with poor potential outcomes would be given more intensive chemotherapy or a bone marrow transplant in an effort to improve their outcome.
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