Activity of certain stem cell genes linked with worse outcomes in acute myeloid leukemia patients
2010-12-22
(Press-News.org) In an examination of leukemic stem cells (LSC), researchers have found that patients with acute myeloid leukemia who had higher activity of certain LSC genes had worse overall, event-free and relapse-free survival, according to a study in the December 22/29 issue of JAMA.
"In many cancers, specific subpopulations of cells appear to be uniquely capable of initiating and maintaining tumors. The strongest support for this cancer stem cell model comes from transplantation assays in immunodeficient mice, which indicate that human acute myeloid leukemia (AML) is driven by self-renewing leukemic stem cells," according to background information in the article. "A major implication of this cancer stem cell model is that the LSCs must be eliminated to eradicate the cancer and cure the patient. While AML was the first human malignancy for which this model gained experimental support, its clinical significance has yet to be fully established."
Andrew J. Gentles, Ph.D., of Stanford University, Palo Alto, Calif., and colleagues examined gene expression (activity) profiles of LSC-enriched (higher concentration) subpopulations from primary AML and normal patient samples. These samples were obtained at a U.S. medical center between April 2005 and July 2007. Other data sets of profiles of AML tumors from 4 independent groups (n = 1,047) also were evaluated.
The researchers found that expression levels of 52 genes distinguished LSC-enriched populations from other subpopulations in cell-sorted AML samples. An LSC score summarizing expression of these genes in primary AML tumor samples was associated with clinical outcomes in the 4 independent patient groups. High LSC scores were associated with worse overall, event-free, and relapse-free survival among patients with either normal karyotypes (set of chromosomes of a cell) or chromosomal abnormalities.
"The absolute risk of death by 3 years was 57 percent for the low LSC score group compared with 78 percent for the high LSC score group. In another cohort with available data on event-free survival for 70 patients with normal karyotypes, the risk of an event by 3 years was 48 percent in the low LSC score group vs. 81 percent in the high LSC score group," the researchers write.
The LSC score was also associated with primary response to induction chemotherapy, because high LSC scores strongly correlated with lower remission rates.
"In this study, we show that a gene expression score associated with the LSC-enriched subpopulation is an independent prognostic factor in AML, with high LSC score associated with adverse outcomes in multiple independent cohorts. … If prospectively validated, the described LSC score may be incorporated into routine clinical practice for predicting prognosis in patients with AML and used in clinical trials incorporating risk-based stratification or randomization strategies."
The researchers add that this study is the first to directly define a signature (a group of genes whose level of activity distinguishes one cell type from another) of enriched AML-initiating cells and to relate this signature to expression profiles of diagnostic specimens, allowing a link to corresponding clinical and pathological features of patients. "Ultimately, this model has major implications for cancer therapy, most notably that in order to achieve cure, the cancer stem cells must be eliminated. To accomplish this in AML, novel therapies targeting LSC must be developed."
###(JAMA. 2010;304[24]:2706-2715. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
To contact corresponding authors Ash A. Alizadeh, M.D., Ph.D., or Ravindra Majeti, M.D., Ph.D., call 650-725-5371 or email Krista Conger at kristac@stanford.edu or Jonathan Rabinovitz at jrabin@stanford.edu
For More Information: Contact the JAMA/Archives Media Relations Department at 312-464-JAMA or email: mediarelations@jama-archives.org.
END
ELSE PRESS RELEASES FROM THIS DATE:
2010-12-22
Stress can enhance ordinary, unrelated memories, a team of neuroscientists has found in a study of laboratory rats. Their results, which appear in the journal PLoS Biology, may bolster our understanding of post-traumatic stress disorder (PTSD) and could offer a pathway for addressing PTSD and related afflictions.
The study was conducted by researchers at the Czech Republic's Academy of Sciences, the State University of New York (SUNY) Downstate Medical Center, and Rockefeller University.
"Our results show that stress can activate memory, even if that memory is unrelated ...
2010-12-22
CHICAGO --- Busy doctors can miss important details about a patient's care during an office examination. To prevent that, Northwestern Medicine researchers have created a whip-smart assistant for physicians – a new system using electronic health records that alerts doctors during an exam when a patient's care is amiss.
After one year, the software program significantly improved primary care physicians' performance and the health care of patients with such chronic conditions as diabetes and cardiovascular disease. The program, a new comprehensive approach tied to a doctor's ...
2010-12-22
The risk of tuberculosis (TB) and latent TB (in which the bacteria that cause TB lie dormant but can reactivate later to cause active TB disease) is higher in the prison population than in the general population. And importantly, the spread of TB and latent TB within prisons can substantially increase their incidence in the general population. These key findings from a systematic review by Iacopo Baussano from the University "Amedeo Avogadro", Italy, and the Imperial College, London, UK, and colleagues and published in this week's PLoS Medicine, suggest that improvements ...
2010-12-22
Earlier initiation of antiretroviral therapy should be the highest priority for global expansion of HIV patient care. This finding, from a paper published in this week's PLoS Medicine, should help resource-limited nations to phase in the implementation of the new 2010 WHO recommendations for HIV treatment. "Immediate scale-up of the entire WHO guideline package may be prohibitively expensive in some settings," said lead author Rochelle P. Walensky, MD, MPH of the Massachusetts General Hospital, Boston, USA. "In many resource-limited settings, the relevant policy question ...
2010-12-22
A study in this week's PLoS Medicine suggests that AIDS patients with cryptococcal meningitis who start HIV therapy are predisposed to immune reconstitution inflammatory syndrome (IRIS) — an exaggerated inflammatory immune response that kills up to one-third of affected people — if they have biomarkers (biochemicals) in their blood showing evidence of a damaged immune system that is not capable of clearing the fungal infection.
David Boulware and Paul Bohjanen from the University of Minnesota, Minneapolis, USA, and their colleagues, David Meya and Andrew Kambugu, at ...
2010-12-22
Despite the growing recognition of the importance of strengthening health systems around the world, there is a considerable lack of shared definitions and guiding principles that are threatening the ability to form strategic policy, practice and evaluations. In this week's PLoS Medicine, Robert Chad Swanson from Brigham Young University, USA and colleagues present a set of 10 guiding principles for health systems strengthening to address this problem, developed from a comprehensive review of the literature and consultation with experts.
"We invite global health leaders ...
2010-12-22
In developing countries where iron deficiency is prevalent, prenatal iron-folic acid supplementation increased offspring intellectual and motor functioning during school age, according to researchers from the Johns Hopkins Bloomberg School of Public Health. They examined the intellectual and motor functioning of children whose mothers received micronutrient supplementation during pregnancy and found that aspects of intellectual functioning including working memory, inhibitory control, and fine motor functioning were positively associated with prenatal iron and folic acid ...
2010-12-22
A new University of British Columbia study has found that people identify the personality traits of people who are physically attractive more accurately than others during short encounters.
The study, published in the December edition of Psychological Science, suggests people pay closer attention to people they find attractive, and is the latest scientific evidence of the advantages of perceived beauty. Previous research has shown that individuals tend to find attractive people more intelligent, friendly and competent than others.
The goal of the study was to determine ...
2010-12-22
TUCSON, Ariz. (December 21, 2010) -- A researcher known widely for his groundbreaking work on the design, manufacture and use of minimally toxic, environmentally friendly chemicals will speak to sustainability practitioners on Jan. 12.
Dr. Paul Anastas, science advisor to the U.S. Environmental Protection Agency (EPA) and assistant administrator for the EPA's Office of Research and Development (ORD), is speaking at the International Congress on Sustainability Science and Engineering, ICOSSE '11, in Tucson, Ariz. This is only the second meeting of ICOSSE and this conference ...
2010-12-22
Researchers from the University of Santiago de Compostela (USC) have analysed levels of radon, a natural radioactive gas, in 58 secondary schools in Galicia. The results show that 34% of these schools exceed the limit of 400 Bequerels/m3 recommended by the European Union. Excessive inhalation of radon is associated with lung cancer.
"Out of all the secondary schools where samples were taken, 34% had radon levels in excess of 400 Bequerels/m3 in some of their classrooms or offices", Juan José Llerena, co-author of the study and a member of the USC's Radiation Analysis ...
LAST 30 PRESS RELEASES:
[Press-News.org] Activity of certain stem cell genes linked with worse outcomes in acute myeloid leukemia patients
