 |
|
Cellular discovery may lead to targeted treatment for rare form of anemia
March 16, 2009CINCINNATI-University of Cincinnati (UC) researchers have identified the specific biological mechanisms believed to lead to a rare and incurable blood disease known as Diamond Blackfan anemia (DBA). Scientists say with further investigation, their discoveries could result in drastic changes to current thinking about treatment for this disease and may lead to promising new drug therapies.
George Thomas, PhD, Stefano Fumagalli, PhD, and collaborators report their findings online ahead of print in the journal Nature Cell Biology on Sunday, March 15, 2009. The research will also appear in the April print issue of the journal and is being presented at the 10th annual International Diamond Blackfan Anemia Consensus Conference in New York, which concludes Monday, March 16.
DBA is a rare blood disorder characterized by the bone marrow's failure to produce red blood cells. This failure is due to an intrinsic defect that makes the red blood cells prone to cell death before they mature. Red blood cells travel through the bloodstream to deliver oxygen to the body's tissues, which is critical to the health and proper function of all tissues.
According to the Centers for Disease Control and Prevention, approximately 25-35 new cases of DBA are diagnosed each year, with the majority of patients being identified before age 1. The most common treatments include blood transfusions and corticosteroids. The disease is characterized by extreme anemia-with a propensity to develop into leukemia-and often has no cure.
Using a preclinical laboratory model, Thomas' team was able to explain how cell death occurs in DBA and identified a specific step in the biological chain of events leading to disease onset where targeted medical intervention may effectively slow-or even stop-red blood cell death.
DBA has recently been attributed to a ribosomal protein defect that the UC team hypothesizes leads to abnormal activation of p53, causing premature death of red blood cells. P53 is a protein that normally functions to trigger "cell suicide" in response to severe cellular damage, therefore protecting the body from overgrowth of defective cells.
Previous research has attributed p53 activation to the passive diffusion of ribosomal protein L11 from the nucleolus, the part of the nucleus where ribosomes are produced to the nucleoplasm.
The UC research, however, suggests that p53 activation is not due to nucleolar breakdown, but is actually the result of an active increase in the production of L11. They suggest that in DBA, a series of L11 interactions results in cell cycle arrest and ultimately leads to cell death and anemia.
"Previous studies suggested L11 was passively coming out of the nucleolus when ribosome production was disrupted. Our study actually showed that the nucleolus stayed intact as ribosomes were still being produced, suggesting selective upregulation of L11," explains Thomas, the John and Gladys Strauss endowed professor of cancer biology at UC and scientific director at UC's Genome Research Institute. "If we can target the L11 interaction, we might be able to spare other stress pathways that mediate potential benefits of p53 induction."
Thomas believes DBA slowly evolves into cancer when this specific molecular checkpoint is lost. This results in the body being genetically reprogrammed over time, leading to the onset of additional medical problems, particularly leukemia, in DBA patients later in life.
"By understanding the chain of biological events leading to this abnormal cell death and targeting the specific molecular checkpoint that controls cell death, we may be able to develop new drugs that would interrupt or stop the process and allow the body to recover, rebuilding healthy bone marrow," adds Thomas.
This research was funded in part by the National Cancer Institute's Mouse Models in Human Cancer Consortium. In addition to Thomas and Funagalli, manuscript co-authors include Sandy Schwemberger, PhD, and George Babcock, MD, and Arti Neb-Gulati of UC; Alessandro Di Cara, PhD of Friedrich Miescher Institute for Biomedical Research in Switzerland; Francois Natt and Jonathan Hall of Novartis Institutes for Biomedical Research in Switzerland; Rosa Bernardi MD, PhD, of San Raffaele, Institute Via Olgettina in Italy; and Pier Paolo Pandolfi, MD, PhD, of Beth Israel Deaconess Medical Center in Boston.
"It is our hope that these discoveries will lead to new treatments for the disease. As anyone can imagine, in any disease where more than 90 percent of patients present before 1 year of age the families clamor for additional breakthroughs," adds Marie Arturi, executive director of the Daniella Maria Arturi Foundation. "We are deeply indebted to all who help in this effort."
University of Cincinnati
According to the Centers for Disease Control and Prevention, approximately 25-35 new cases of DBA are diagnosed each year, with the majority of patients being identified before age 1. The most common treatments include blood transfusions and corticosteroids. The disease is characterized by extreme anemia-with a propensity to develop into leukemia-and often has no cure.
Using a preclinical laboratory model, Thomas' team was able to explain how cell death occurs in DBA and identified a specific step in the biological chain of events leading to disease onset where targeted medical intervention may effectively slow-or even stop-red blood cell death.
DBA has recently been attributed to a ribosomal protein defect that the UC team hypothesizes leads to abnormal activation of p53, causing premature death of red blood cells. P53 is a protein that normally functions to trigger "cell suicide" in response to severe cellular damage, therefore protecting the body from overgrowth of defective cells.
Previous research has attributed p53 activation to the passive diffusion of ribosomal protein L11 from the nucleolus, the part of the nucleus where ribosomes are produced to the nucleoplasm.
The UC research, however, suggests that p53 activation is not due to nucleolar breakdown, but is actually the result of an active increase in the production of L11. They suggest that in DBA, a series of L11 interactions results in cell cycle arrest and ultimately leads to cell death and anemia.
"Previous studies suggested L11 was passively coming out of the nucleolus when ribosome production was disrupted. Our study actually showed that the nucleolus stayed intact as ribosomes were still being produced, suggesting selective upregulation of L11," explains Thomas, the John and Gladys Strauss endowed professor of cancer biology at UC and scientific director at UC's Genome Research Institute. "If we can target the L11 interaction, we might be able to spare other stress pathways that mediate potential benefits of p53 induction."
Thomas believes DBA slowly evolves into cancer when this specific molecular checkpoint is lost. This results in the body being genetically reprogrammed over time, leading to the onset of additional medical problems, particularly leukemia, in DBA patients later in life.
"By understanding the chain of biological events leading to this abnormal cell death and targeting the specific molecular checkpoint that controls cell death, we may be able to develop new drugs that would interrupt or stop the process and allow the body to recover, rebuilding healthy bone marrow," adds Thomas.
This research was funded in part by the National Cancer Institute's Mouse Models in Human Cancer Consortium. In addition to Thomas and Funagalli, manuscript co-authors include Sandy Schwemberger, PhD, and George Babcock, MD, and Arti Neb-Gulati of UC; Alessandro Di Cara, PhD of Friedrich Miescher Institute for Biomedical Research in Switzerland; Francois Natt and Jonathan Hall of Novartis Institutes for Biomedical Research in Switzerland; Rosa Bernardi MD, PhD, of San Raffaele, Institute Via Olgettina in Italy; and Pier Paolo Pandolfi, MD, PhD, of Beth Israel Deaconess Medical Center in Boston.
"It is our hope that these discoveries will lead to new treatments for the disease. As anyone can imagine, in any disease where more than 90 percent of patients present before 1 year of age the families clamor for additional breakthroughs," adds Marie Arturi, executive director of the Daniella Maria Arturi Foundation. "We are deeply indebted to all who help in this effort."
University of Cincinnati
Anemia Current Events and Anemia News RSSMortality Rates Reduced among Children Whose Mothers Received Iron-folic Acid Supplements
Offspring whose mothers had been supplemented with iron-folic acid during pregnancy had dramatically reduced mortality through age 7, according to researchers at the Johns Hopkins Bloomberg School of Public Health.
Experts unveil new CVD guidelines and position papers
Several new guidelines and position papers offering the most up to date information to ensure that clinicians practice evidence-based medicine were released at the Canadian Cardiovascular Congress 2009 this week.
Mayo Clinic study shows people with heart devices can 'digest' advanced diagnostic technology safely
A new Mayo Clinic study suggests that video capsule endoscopy (CE), a procedure that uses wireless technology in diagnosing intestinal disease, is safe for patients with heart devices.
Common weed could provide clues on aging and cancer
A common weed and human cancer cells could provide some very uncommon details about DNA structure and its relationship with telomeres and how they affect cellular aging and cancer, according to a team led by scientists from Texas A&M University and the University of Cincinnati (UC).
Designer molecule detects tiny amounts of cyanide, then glows
A small molecule designed to detect cyanide in water samples works quickly, is easy to use, and glows under ultraviolet or "black" light.
American Dietetic Association supports IOM recommendations on school meal programs
The American Dietetic Association welcomes a report issued Wednesday, October 21, by the Institute of Medicine encouraging federal school meal programs to adopt standards that increase the nutrition content and limit the calories in meals served to schoolchildren.
Better blood screening process needed to prevent babesiosis transmission
Babesiosis is a potentially dangerous parasitic disease transmitted by ticks and is common in the Northeast and the upper Midwest. Babesia lives inside of red blood cells, meaning it can also be transmitted through a blood transfusion from an infected but otherwise asymptomatic blood donor.
Governor recognizes stem cell research at Einstein
Albert Einstein College of Medicine of Yeshiva University hosted a roundtable discussion on stem cell research with New York Governor David A. Paterson today.
Anemic Patients With MDS Gain Long-Term Benefits From Erythropoietin and Myeloid Growth Factor Hormones
Myelodysplastic syndromes (MDS), a group of blood disorders that can lead to acute myeloid leukemia (AML) in some patients, often cause severe anemia (when the body lacks a sufficient number of functional red blood cells).
Mutation in renin gene linked to inherited kidney disease
A mutation in a gene that helps regulate high blood pressure is a cause of inherited kidney disease, according to a new study by researchers at Wake Forest University School of Medicine, Charles University in Prague and colleagues.
More Anemia Current Events and Anemia News Articles
 |
Anemia in Women: Self-Help and Treatment by M.D. Joan Gomez (Author) Many women are unaware that they have anemia. Its symptoms — fatigue, weakness, shortness of breath, headaches, and poor concentration — are often attributed to stress rather than iron deficiency. Using case studies, Joan Gomez discusses the prevention and treatment of anemia during childhood, adolescence, and menopause. |
 |
The Iron Disorders Institute Guide to Anemia by Cheryl Garrison (Author) More than 2 billion people worldwide have some form of anemia. Even so, the condition is greatly misunderstood and often improperly treated. The Iron Disorders Institute Guide to Anemia contains everything a patient needs to know about the different forms of anemia, symptoms, treatment, and diet. It provides patients and family members with everything they need to be proactive with their physicians, including information about what doctors must do to differentiate between different causes and how each cause is treated. |
 |
Understanding Anemia (Understanding Sickness & Health Series) by M.D., Ed Uthman (Author) Each year thousands are told they suffer from anemia, but most have only a vague understanding of the condition. In fact, "anemia" is a generic term that includes myriad specific diseases, each of which has its own story regarding cause, manifestations, and treatments. Understanding Anemia gently builds upon elementary knowledge of biology to provide the general reader with a fairly sophisticated understanding of the various causes of anemia, of the methods used to make diagnoses, and of the principles of treatment. The book begins with a definition of anemia and a brief history of the scientific study of blood. It explains how the doctor makes the diagnosis and details the main types of anemia. Since the different conditions result from the failure of... |
 |
Nature's Plus - Hema-Plex, 30 tablets by Nature's Plus |
 |
Aenima by Tool No Description Available Track: 10: Die Eier Von Satan,Track: 11: Pushit,Track: 12: Cesaro Summability,Track: 13: Aenema,Track: 14: (-) Ions,Track: 15: Third Eye,Track: 1: Stinkfist,Track: 2: Eulogy,Track: 3: H.,Track: 4: Useful Idiot,Track: 5: Forty Six And 2,Track: 6: Message To Harry Manback,Track: 7: Hooker With A Penis,Track: 8: Intermission,Track: 9: Jimmy Media Type: CD Artist: TOOL Title: AENIMA Street Release Date: 10/01/1996 |
 |
Heavy Menstrual Flow and Anemia: Self Help Book by Susan M. Lark (Author) Most women have experienced unusually heavy menstrual bleeding at one time or another in their lives. But for millions of American women, heavy menstrual flow and the debilitating effects of anemia are chronic problems. Because it isn't enough to treat only the symptoms, Dr. Lark examines the underlying causes associated with these conditions, analyzes the risk factors for different groups of women, and presents a comprehensive self-assessment program. She discusses the vital roles of diet and exercise in coping with heavy menstrual flow and anemia, as well as the most current medical treatment and drug therapies available. |
 |
Biosafe Anemia Meter, Red (1 test) by Biosafe The Anemia Meter is the world's first single use rapid response Anemia Device! The test provides you with an accurate, convenient, and inexpensive way to test for possible anemia in the comfort and safety of your home or office. Low hemoglobin levels are associated with extreme weakness, fatigue, shortness of breath, dizziness, depression, rapid heart beat, and/or pale skin. People over 65, those who have had recent surgery, and HIV/AIDS patients are at increased risk. Additionally, people who have kidney disease, diabetes, rheumatoid arthritis, cancer, or heart disease should check their hemoglobin level regularly. The specimen collection process is quick, easy and virtually painless. Using the special lancet (included with the BIOSAFE Anemia Meter), one or more drops of blood are taken... |
 |
Anemias and Other Red Cell Disorders by Kenneth Bridges (Author), Howard A. Pearson (Author) The first comprehensive, yet concise, clinical guide to the full spectrum of anemias Anemias and Other Red Cell Disorders is the first resource to provide a practical diagnostic/treatment framework for identifying and successfully managing acute, congenital, and chronic anemias, and other red blood cell disorders. With its broad scope, easy-to-navigate format, and ready-to-apply diagnostic and treatment strategies, this is the most accessible - and essential - guide to anemias and related diseases ever published. Features A complete top-to-bottom review of anemias, written with the non-specialist in mind Logical chapter organization based on the clinical features that prompt the initial encounter between doctor and patient Discussions... |
 |
Cancer Patients and Anemia Part of the award winning public television series Healthy Body/Healthy Mind. Anemia (an abnormally low number of red blood cells) is a common condition in cancer patients that may occur either as a direct result of the cancer or as a side effect of the cancer treatment. Chemotherapy, radiation therapy, and blood loss during surgery are all common causes of anemia in cancer patients. But, as you'll see in this program, anemia can be successfully treated, and patients can go on to beat their cancers and live healthy lives. |
 |
Anemia In Your Sheets Still Remains (Primary Contributor) |
| © 2009 BrightSurf.com |