Researchers at Albert Einstein College of Medicine of Yeshiva University have found that abnormal bone marrow stem cells drive the development of myelodysplastic syndromes (MDS), serious blood diseases that are common among the elderly and that can progress to acute leukemia. The findings could lead to targeted therapies against MDS and prevent MDS-related cancers. The study is published today in the online edition of the journal Blood.
"Researchers have suspected that MDS is a 'stem cell disease,' and now we finally have proof," said co-senior author Amit Verma, M.B.B.S., associate professor of medicine and of developmental and molecular biology at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care. "Equally important, we found that even after MDS standard treatment, abnormal stem cells persist in the bone marrow. So, although the patient may be in remission, those stem cells don't die and the disease will inevitably return. Based on our findings, it's clear that we need to wipe out the abnormal stem cells in order to improve cure rates."
MDS are a diverse group of incurable diseases that affect the bone marrow and lead to low numbers of blood cells. While some forms of MDS are mild and easily managed, some 25 to 30 percent of cases develop into an aggressive disease called acute myeloid leukemia. Each year, about 10,000 to 15,000 people in the U.S. are diagnosed with MDS, according to the National Marrow Donor Program.
Most cases of MDS occur in people over age 60, but the disease can affect people of any age and is more common in men than women. Symptoms vary widely, ranging from anemia to infections, fever and bleeding. Treatment usually involves chemotherapy to destroy abnormal blood cells plus supportive care such as blood transfusions.
In the current study, lead author Britta Will, Ph.D., research associate in the department of cell biology, and her colleagues analyzed bone marrow stem cells and progenitor cells (i.e., cells formed by stem cells) from 16 patients with various types of MDS and 17 healthy controls. The stem and progenitor cells were isolated from bone marrow using novel cell-sorting methods developed in the laboratory of co-senior author Ulrich Steidl, M.D., Ph.D., assistant professor of cell biology and of medicine and the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein.
Genome-wide analysis revealed widespread genetic and epigenetic alterations in stem and progenitor cells taken from MDS patients, in comparison to cells taken from healthy controls. The abnormalities were more pronounced in patients with types of MDS likely to prove fatal than in patients with lower-risk types.
"Our study offers new hope that MDS can be more effectively treated, with therapies that specifically target genes that are deregulated in early stem and progenitor cells," said Dr. Steidl. "In addition, our findings could help to detect minimal residual disease in patients in remission, allowing for more individualized treatment strategies that permanently eradicate the disease."
The paper is titled, "Stem and progenitor cells in myelodysplastic syndromes show aberrant stage specific expansion and harbor genetic and epigenetic alterations." Other Einstein contributors include: Li Zhou, Ph.D., Thomas O. Vogler, B.Sc., Carolina Schinke, M.D., Roni Tamari, M.D., Yiting Yu, Ph.D., Tushar Bhagat, M.S., Sanchari Bhattacharyya, Ph.D., Laura Barreyro, M.S., Christoph Heuck, M.D., Yongkai Mo, Ph.D., Samir Parekh, M.D., Christine McMahon, M.D., Cristina Montagna, Ph.D., John Greally, M.B.B.Ch., Ph.D., and B. Hilda Ye, Ph.D. Other contributors include: Susana Ben-Neriah and Christian Steidl, M.D., at University of British Columbia, Vancouver, BC, Canada; Andrea Pellagatti, Ph.D., and Jacqueline Boultwood, Ph.D., at John Radcliffe Hospital, Oxford, UK; Lewis Silverman, M.D., at Mt. Sinai School of Medicine, New York, NY; Jaroslaw Maciejewski, M.D., Ph.D., at Cleveland Clinic, Cleveland, OH; and Alan F. List, M.D. at Moffitt Cancer Center, Tampa, FL.
The research was supported by grants from the National Heart, Lung, and Blood Institute (HL082946) and the National Cancer Institute (CA131503), both part of the National Institutes of Health.
Albert Einstein College of Medicine
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. In 2011, Einstein received nearly $170 million in awards from the NIH for major research centers at Einstein in diabetes, cancer, liver disease, and AIDS, as well as other areas. Through its affiliation with Montefiore Medical Center, the University Hospital for Einstein, and four other hospital systems, the College of Medicine runs one of the largest post-graduate medical training programs in the United States, offering 155 residency programs to more than 2,200 physicians in training. For more information, please visit www.einstein.yu.edu and follow us on Twitter @EinsteinMed.
Montefiore Medical Center
As the University Hospital for Albert Einstein College of Medicine, Montefiore is a premier academic medical center nationally renowned for its clinical excellence, scientific discovery and commitment to its community. Montefiore is consistently recognized among the top hospitals nationally by U.S. News & World Report, and excels at educating tomorrow's healthcare professionals in superior clinical and humanistic care. Linked by advanced technology, Montefiore is a comprehensive and integrated health system that derives its inspiration for excellence from its patients and community. For more information, please visit www.montefiore.org and www.montekids.org and follow us on Twitter @MontefioreNews.
Kim Newman | EurekAlert!
A new molecular player involved in T cell activation
07.12.2018 | Tokyo Institute of Technology
News About a Plant Hormone
07.12.2018 | Julius-Maximilians-Universität Würzburg
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.
Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...
New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals
Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.
Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.
Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...
Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.
The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.
06.12.2018 | Event News
03.12.2018 | Event News
28.11.2018 | Event News
07.12.2018 | Life Sciences
07.12.2018 | Materials Sciences
07.12.2018 | Physics and Astronomy