 |
|
Study identifies molecular process underlying leukemia
August 22, 2006CHAPEL HILL - New research from the University of North Carolina at Chapel Hill has identified a molecular process in cells that is crucial to the development of two common leukemias. The findings help explain how fundamental cell processes go awry during cancer development and represent a first step toward new, targeted treatments for leukemia.
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) leukemias develop when certain chromosomal abnormalities disrupt the genes that control blood cell formation. Without the proper instructions from these genes, blood cells produced by bone marrow never fully mature; these immature cells, which can't carry vital nutrients or fight infection, then flood the body.
The researchers showed how a fusion of proteins created by flawed chromosomes can trigger leukemia development. The study also identified an enzyme's important role in this process.
The results were published online Aug. 20 and will appear in a future print issue of the journal Nature Cell Biology.
The research was led by Dr. Yi Zhang, professor of biochemistry and biophysics in the UNC School of Medicine and a Howard Hughes Medical Institute Investigator. Zhang is also a member of the UNC Lineberger Comprehensive Cancer Center. The work was supported by grants from the National Institutes of Health.
The study examined chromosomal translocation, in which a fragment of a chromosome breaks off and joins another. Chromosomes are the cellular structures that carry DNA. Translocation along chromosomes can result in the generation of fusion proteins that often "misregulate" specific genes, including genes that can cause leukemia, and is a common cause of leukemia, Zhang said. The most common chromosome translocations found in leukemia patients involve the mixed lineage leukemia gene, MLL. One of the fusion proteins that partners with MLL in leukemia is AF10.
AF10 has been shown to fuse with another protein, CALM, in patients with acute lymphoblastic leukemia or acute myeloid leukemia. But it has been unclear whether that fusion could cause leukemia, and little is known about how this CALM-AF10 fusion may lead to the disease, Zhang said. "Results from this study provide important insights into these questions," he said.
Zhang and his colleagues showed that the CALM-AF10 fusion is "necessary and sufficient" for cellular transformation to leukemia in a mouse model of the disease. They also discovered that the fusion overactivates (also called upregulation) the gene HoxA5. Moreover, upregulation of the HoxA5 gene is necessary for cellular transformation to leukemia, the study shows.
Overactive Hox genes are known to play a role in cancer, Zhang said. "In mammals, Hox genes play an important role in embryonic development. They help set the developmental pattern. They also play a role in cancer. That's why their expression must be tightly controlled."
The researchers also identified an enzyme, hDOT1L, as important for upregulating gene expression by the CALM-AF10 fusion protein.
This finding builds on earlier work by the Zhang laboratory involving another fusion protein, MLL-AF10, and the enzyme's upregulation of the Hox gene HoxA9.
Having demonstrated the role of hDOT1L in leukemia development of two different fusion proteins, the Zhang lab is exploring the possibility of developing drugs that target the hDOT1L enzyme. \\\
University of North Carolina School of Medicine
The results were published online Aug. 20 and will appear in a future print issue of the journal Nature Cell Biology.
The research was led by Dr. Yi Zhang, professor of biochemistry and biophysics in the UNC School of Medicine and a Howard Hughes Medical Institute Investigator. Zhang is also a member of the UNC Lineberger Comprehensive Cancer Center. The work was supported by grants from the National Institutes of Health.
The study examined chromosomal translocation, in which a fragment of a chromosome breaks off and joins another. Chromosomes are the cellular structures that carry DNA. Translocation along chromosomes can result in the generation of fusion proteins that often "misregulate" specific genes, including genes that can cause leukemia, and is a common cause of leukemia, Zhang said. The most common chromosome translocations found in leukemia patients involve the mixed lineage leukemia gene, MLL. One of the fusion proteins that partners with MLL in leukemia is AF10.
AF10 has been shown to fuse with another protein, CALM, in patients with acute lymphoblastic leukemia or acute myeloid leukemia. But it has been unclear whether that fusion could cause leukemia, and little is known about how this CALM-AF10 fusion may lead to the disease, Zhang said. "Results from this study provide important insights into these questions," he said.
Zhang and his colleagues showed that the CALM-AF10 fusion is "necessary and sufficient" for cellular transformation to leukemia in a mouse model of the disease. They also discovered that the fusion overactivates (also called upregulation) the gene HoxA5. Moreover, upregulation of the HoxA5 gene is necessary for cellular transformation to leukemia, the study shows.
Overactive Hox genes are known to play a role in cancer, Zhang said. "In mammals, Hox genes play an important role in embryonic development. They help set the developmental pattern. They also play a role in cancer. That's why their expression must be tightly controlled."
The researchers also identified an enzyme, hDOT1L, as important for upregulating gene expression by the CALM-AF10 fusion protein.
This finding builds on earlier work by the Zhang laboratory involving another fusion protein, MLL-AF10, and the enzyme's upregulation of the Hox gene HoxA9.
Having demonstrated the role of hDOT1L in leukemia development of two different fusion proteins, the Zhang lab is exploring the possibility of developing drugs that target the hDOT1L enzyme. \\\
University of North Carolina School of Medicine
Leukemia Current Events and Leukemia News RSSNew research into the mechanisms of gene regulation
A team led by Penn State's Ross Hardison, T. Ming Chu Professor of Biochemistry and Molecular Biology, has taken a large step toward unraveling how regulatory proteins control the production of gene products during development and growth.
UAB Researchers Discover Antibody Receptor Identity, Propose Renaming Immune-System Gene
Researchers at the University of Alabama at Birmingham (UAB) have uncovered the genetic identity of a cellular receptor for the immune system's first-response antibody, a discovery that sheds new light on infection control and immune disorders.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
Aileron collaborates study in Nature: Stapled peptides inhibit Notch1 transcription factor
This research validates the potential for Stapled Peptides to modulate key intracellular biological targets, such as transcription factors, that have not been addressable with current small molecule or biologic drug modalities.
Researchers 'notch' a victory toward new kind of cancer drug
Scientists have devised an innovative way to disarm a key protein considered to be "undruggable," meaning that all previous efforts to develop a drug against it have failed.
FDA approved leukemia drugs shows promise in ovarian cancer cells
The drug Sprycel, approved for use by the U.S. Food and Drug Administration in patients with chronic myeloid leukemia, significantly inhibited the growth and invasiveness of ovarian cancer cells and also promoted their death, a study by researchers with UCLA's Jonsson Comprehensive Cancer Center found.
First use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
American Dietetic Association Releases Updated Position Paper Promoting and Supporting Breastfeeding
The American Dietetic Association has released an updated position paper on breastfeeding that details health benefits for both infants and mothers and encourages promotion of breastfeeding whenever possible.
Drug shows promise in treating dangerous complication of erectile disorder
Thousands of men are afflicted with an embarrassing and painful condition that triggers spontaneous, long-lasting erections. There are limited treatment options, but a solution could be on the way thanks to new research at The University of Texas Health Science Center at Houston.
Brain tumors in childhood leave a lasting mark on cognition, life status
Brain tumors in childhood cast a long shadow on survivors. The first study of the lasting impact of these tumors -- the most common solid malignancies in childhood -- shows that survivors have ongoing cognitive problems.
More Leukemia Current Events and Leukemia News Articles
 |
100 Q&A About Leukemia, Second Edition (100 Questions & Answers about) by Edward D. Ball (Author) This book deals with leukemia from a doctor's and a patient's perspective. |
 |
Childhood Leukemia: A Guide for Families, Friends and Caregivers (3rd Edition) by Nancy Keene (Author) This most complete parent guide available covers not only detailed and precise medical information about leukemia and the various treatment options, but also day-to-day practical advice on how to cope with procedures, hospitalization, family and friends, school, social and financial issues, communication, feelings, and, if therapy is not successful, the difficult issues of death and bereavement. Woven among the medical details and the practical advice are the voices of parents and children who have lived with leukemia and its treatments. As many parents have already found, advice from "veteran" parents can be a lifeline.This third edition contains significant updates to the information on treatments, chemotherapy drugs, bone marrow transplants, coping with side effects, and resources. It... |
 |
Adult Leukemia: A Comprehensive Guide for Patients and Families by Barbara Lackritz (Author) For the tens of thousands of Americans with adult leukemia, the condition, which is really a group of diseases, is often a baffling one for patients and families to understand, and finding targeted information on individual conditions can be difficult. In straightforward language, Adult Leukemia: A Comprehensive Guide for Patients and Families addresses: Diagnosis and medical testsFinding a good oncologistTreatmentsSide effectsEmotional responses to diagnosis, treatment, remission, possible recurrenceGetting support from your family, friends, employers, and the broader community Author Barb "Grannybarb" Lackritz is a leading patient activist in the leukemia community and herself a long-term leukemia survivor. She emphasizes the promising emerging treatments for leukemia, covering in... |
 |
Leukemia Awareness Green Genuine Swarovski Crystal Bracelet by SilverSpeck.com This Beautiful Green Genuine Swarovski Crystal Bracelet Is the Perfect Bracelet you have been waiting for. It has a Sparking Glimmer and is beaded on a Comfort Stretch band. Looks great when worn with a few at a time or alone. Crystal beads can also be used to create your own jewelry! Very Stylish and Pretty! |
 |
Understanding MDS/Leukemia Part of the award winning public television series Healthy Body/Healthy Mind. It can begin as a harmless case of fatigue but can lead to a blood transfusion or possible bone marrow transplant. It's a disease virtually unknown to the general public and often not diagnosed by medical caregivers. Mylodysplastic syndrome, or MDS, is a disorder of the bone marrow and can lead to leukemia and eventually death. In this program, success stories abound as researchers struggle to find answers. This product is manufactured on demand using DVD-R recordable media. Amazon.com's standard return policy will apply. |
 |
Fight Against Acute Lymphoblastic Leukemia Long Sleeve T-shirt Large White by Shop Zeus |
 |
Leukemia (The Biology of Cancer) by Donna M. Bozzone (Author) This book includes full-color photographs, glossary, sidebars, further reading, web sites, references, and an index. Leukemia, or cancer of the blood or bone marrow, occurs in both acute and chronic forms. While the exact causes of the disease are not known, several risk factors have been identified. There are four major types of leukemia: acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoid leukemia (ALL), and chronic lymphoid leukemia (CLL), and treatments include chemotherapy, radiation, and bone marrow transplants. "Leukemia" discusses the science of leukemia, theories about its causes, the history of the disease, and the current treatments and how they work. |
|
Suck My Heaven by Leukemia | |
 |
Leukemia (Dub Makers Remix) ResiveR (Primary Contributor) |
 |
Assure FeLv Feline Leukemia Virus Antigen Test Kit 25 tests by Synbiotics Corporation A non-invasive saliva test accurate enough for general FeLv testing, pre-vaccination & health screens. Ideal for detection of viral shedding or to confirm blood ELISA positives. This versatile diagnostic tool utilizes saliva, whole blood, plasma or serum. Pre-measured reagents plus your sample. Must be refrigerated until ready to use. Warm to room temp before using. |
| © 2009 BrightSurf.com |