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NCI scientists create model that predicts follicular lymphoma survival
Scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, have created a model that
predicts the survival of follicular lymphoma patients based on the molecular characteristics of their tumors at diagnosis.
The model is based on two sets of genes--called survival-associated signatures--whose activity was found to be associated
with good or poor prognosis for patients with the cancer. The scientists' results, to be published in the November 19, 2004,
New England Journal of Medicine*, suggest that immune cells infiltrating follicular lymphoma tumors have an important impact
on survival--both signatures came from such immune cells.
The progression rate of follicular lymphoma, the most common non-Hodgkin lymphoma, varies widely. "In some patients the
disease progresses slowly over many years, whereas in others progression is rapid, with the cancer transforming into
aggressive lymphoma and leading to early death," explained principle investigator Louis M. Staudt, M.D., Ph.D., of NCI's
Center for Cancer Research. "Understanding the molecular causes of such differences in survival could provide a more accurate
method to determine patient risk, which could be used to guide treatment and may suggest new therapeutic approaches."
To create their model, Staudt and associates used follicular lymphoma biopsies taken from 191 untreated patients. The
biopsies were taken between 1974 and 2001 and came from North American and European institutions that are part of the
NCI-sponsored Lymphoma/Leukemia Molecular Profiling Project**. Following their biopsies, all patients received standard
treatments. The NCI scientists examined their subsequent medical records to determine survival. Biopsies were divided into
two groups balanced for survival and institution: 95 went into a group used to uncover gene expression patterns associated
with survival; the other 95 were used to test the predictive power of these patterns.
NCI scientists first used a DNA micro array to determine which genes were expressed (active) in the first group of 95 tumor
biopsies, and at what levels. They then determined which of these genes were statistically associated with survival. They
called those associated with long survival "good prognosis genes" and those associated with short survival "poor prognosis
genes."
Next, the researchers identified subsets of both kinds of genes that tended to be expressed together. These they named
"survival-associated signatures." Two signatures--one which indicated poor prognosis, the other good--had strong synergy and
together predicted survival better than any other model tested. Unexpectedly, both came from nonmalignant immune cells
infiltrating the tumors. The good prognosis signature genes reflect a mixture of immune cells that is dominated by T cells. T
cells react to specific threats to the body's health. In contrast, the poor prognosis signature genes reflect a different
group of immune cells dominated by macrophages and/or dendritic cells--which react to nonspecific threats--rather than T
cells.
The two signature model allowed NCI scientists to divide patients into four equal groups with disparate average survival
rates of 3.9, 10.8, 11.1, and 13.6 years. For the 75 percent of patients with survival rates 10 years or longer, "watchful
waiting is appropriate," Staudt said. "These patients would benefit from knowing that they may not need treatment for quite
some time. On the other hand, those patients in the group with the lowest survival rate should be considered for newer
treatments and clinical trials," added Staudt.
The fact that the most predictive signatures came from immune cells suggests an important interplay between the host immune
system and malignant cells in follicular lymphoma. "One possibility is that the immune cells with the good-prognosis
signature are attacking the lymphoma and keeping it in check," Staudt speculated. "Another possibility is that these immune
cells may provide signals that encourage the cancer cells not to leave the lymph node, preventing or delaying the spread of
the cancer," he added. Knowing more about the signals that may delay the spread of follicular lymphoma could provide new
therapeutic targets.
For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information
Service at 1-800-4-CANCER (1-800-422-6237).
* Dave SS, Wright G, et al. A Molecular Predictor of Survival Following Diagnosis of Follicular Lymphoma Based on the Profile
of Non-Malignant Tumor-Infiltrating Immune Cells. New England Journal of Medicine. November 18, 2004.
** Participating institutions in the Lymphoma/Leukemia Molecular Profiling Project include: Center for Cancer Research,
National Cancer Institute, USA; University of Nebraska Medical Center, USA; Southwest Oncology Group, USA; British Columbia
Cancer Agency, Canada; Norwegian Radium Hospital, Norway; University of Wuerzburg, Germany; University of Barcelona, Spain;
and St. Bartholomew's Hospital, UK.
Contact: NCI Press Officers
ncipressofficers@mail.nih.gov
301-496-6641
NIH/National Cancer Institute
http://www.nci.nih.gov
NCI oameni de ºtiinþã a crea model prezice cã follicular lymphoma supravieþuire - NCI scientists create model that predicts follicular lymphoma survival - articole medicale engleza - startsanatate