Research team uncovers root cause of multiple myeloma relapse

Findings provide insights for new, targeted cancer therapies in clinical trials

2013-09-18

(Press-News.org) PHOENIX, Ariz. — Sept. 18, 2013 — Researchers have discovered why multiple myeloma, a difficult to cure cancer of the bone marrow, frequently recurs after an initially effective treatment that can keep the disease at bay for up to several years.

Working in collaboration with colleagues at Princess Margaret Hospital in Toronto, researchers from Mayo Clinic in Arizona and the Translational Genomics Research Institute (TGen) in Phoenix were part of the team that conducted the study published in the Sept. 9 issue of Cancer Cell.

The research team initially analyzed 7,500 genes in multiple myeloma cells to identify genes which when suppressed made cancer cells resistant to a common class of drugs called proteasome inhibitors such as bortezomib or carfilzomib. Then, the team studied bone marrow biopsies from patients to further understand their results. The process identified two genes (IRE1 and XBP1) that control response to the proteasome inhibitor and the mechanism underlying the drug resistance that is the barrier to cure.

The findings showed recurrence was due to an intrinsic resistance found in immature tumor progenitor (mother) cells is the root cause of the disease and also spawns relapse. The research demonstrates that although the visible cancer cells that make up most of the tumor are sensitive to the proteasome inhibitor drug, the underlying progenitor cells are untouched by this therapy. These progenitor cells then proliferate and mature to reboot the disease process, even in patients who appeared to be in complete remission.

"Our findings reveal a way forward toward a cure for multiple myeloma, which involves targeting both the progenitor cells and the plasma cells at the same time," says Rodger Tiedemann, M.D., a hematologist specializing in multiple myeloma and lymphoma at Princess Margaret. "Now that we know that progenitor cells persist and lead to relapse after treatment, we can move quickly into clinical trials, measure this residual disease in patients, and attempt to target it with new drugs or with drugs that may already exist."

"Some myeloma cells are too immature to be caught by the drugs and thus hide underground only to reemerge later," says Keith Stewart, M.B., Ch.B., Dean for Research at Mayo Clinic in Arizona and contributor to the study. "This study has wide implications in the search for a cure of this common blood cancer as this 'progenitor cell' will have to be targeted."

Jonathan Keats, Ph.D., head of TGen's Multiple Myeloma Research Laboratory, said: "This study, which leverages data generated at TGen as part of the Multiple Myeloma Genomics Initiative, shows how mutations acquired by multiple myeloma tumors can make a tumor resistant to specific therapies and highlights the importance of TGen's precision medicine approaches."

Dr. Tiedemann says: "If you think of multiple myeloma as a weed, then proteasome inhibitors are like a goat that eats the mature foliage above ground, producing a remission, but doesn't eat the roots, so that one day the weed returns."

### The study — Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma — was funded by the National Cancer Institute, Multiple Myeloma Research Foundation, Leukemla and Lymphoma Society and Canadian Cancer Society, the Arthur Macaulay Cushing Estate and The Princess Margaret Cancer Foundation.

Dr. Tiedemann is the Molly and David Bloom Chair in Multiple Myeloma Research, at the University of Toronto, Dr. Stewart is the Anna Maria and Vasek Pollack Professor of Cancer Research at Mayo Clinic. Dr. Keats is an Assistant Professor in TGen's Integrated Cancer Genomics Division.

About Mayo Clinic Mayo Clinic is a nonprofit worldwide leader in medical care, research, and education for people from all walks of life. For more information, visit http://www.mayoclinic.org/about/ and http://www.mayoclinic.org/news. Journalists can become a member of the Mayo Clinic News Network for the latest health, science and research news and access to video, audio, text and graphic elements that can be downloaded or embedded.

Media Contact: Jim McVeigh, Mayo Clinic
480-301-4222
Mcveigh.jim@mago.edu

About TGen Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with cancer, neurological disorders and diabetes, through cutting edge translational research (the process of rapidly moving research towards patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: http://www.tgen.org.

Press Contact: Steve Yozwiak
TGen Senior Science Writer
602-343-8704
syozwiak@tgen.org

ELSE PRESS RELEASES FROM THIS DATE:

Moderate exercising encourages a healthier lifestyle

2013-09-18

The obesity epidemic has massive socio-economic consequences, and decades of health campaigns have not made significant headway. Researchers at the University of Copenhagen are therefore pursuing the development of new, interdisciplinary methods for preventing and treating this widespread problem. The subjects in the test group that exercised the least talk about increased energy levels and a higher motivation for exercising and pursuing a healthy everyday life. "Obesity is a complex social problem requiring a multidisciplinary approach. In a new scientific article ...

Signal gradients in 3-D guide stem cell behavior

2013-09-18

Scientists know that physical and biochemical signals can guide cells to make, for example, muscle, blood vessels or bone. But the exact recipes to produce the desired tissues have proved elusive. Now, researchers at Case Western Reserve University have taken a step toward identifying that mix by developing an easy and versatile way of forming physical and biochemical gradients in three dimensions. Ultimately, one of their goals is to engineer systems to manipulate stem cells to repair or replace damaged tissues and organs. "If we can control the spatial presentation ...

Services lacking for young gay black men

2013-09-18

EAST LANSING, Mich. -- Physical, sexual and emotional abuse among young gay black men is a pervasive problem, yet there remains a lack of social services and resources available to help them, a Michigan State University scholar argues in a new study. The trauma they experience -- often at a young age -- is related to depression, substance abuse and high-risk sexual behavior, said Robin Lin Miller, professor of psychology. "Young black men who are gay and bisexual have few resources available to them that are tailored to their specific needs and concerns, despite how ...

Study: Different hormone therapy formulations may pose different risks for heart attack and stroke

2013-09-18

LOS ANGELES (Embargoed Until 9 a.m. EDT/6 a.m. PDT on Sept. 18, 2013) – Post-menopausal women whose doctors prescribe hormone replacement therapy for severe hot flashes and other menopause symptoms may want to consider taking low doses of Food and Drug Administration-approved bioidentical forms of estrogen or getting their hormones via a transdermal patch. A new observational study shows bioidentical hormones in transdermal patches may be associated with a lower risk of heart attack and FDA-approved products -- not compounded hormones -- may be associated with a slightly ...

4 new species of 'legless lizards' discovered living on the edge

2013-09-18

California biologists have discovered four new species of reclusive legless lizards living in some of the most marginal habitat in the state: a vacant lot in downtown Bakersfield, among oil derricks in the lower San Joaquin Valley, on the margins of the Mojave desert, and at the end of one of the runways at LAX. "This shows that there is a lot of undocumented biodiversity within California," said Theodore Papenfuss, a reptile and amphibian expert, or herpetologist, with UC Berkeley's Museum of Vertebrate Zoology, who discovered and identified the new species with James ...

Southern Ocean sampling reveals travels of marine microbes

2013-09-18

SYDNEY: By collecting water samples up to six kilometres below the surface of the Southern Ocean, UNSW researchers have shown for the first time the impact of ocean currents on the distribution and abundance of marine micro-organisms. The sampling was the deepest ever undertaken from the Australian icebreaker, RSV Aurora Australis. Microbes are so tiny they are invisible to the naked eye, but they are vital to sustaining life on earth, producing most of the oxygen we breathe, soaking up carbon dioxide from the atmosphere and recycling nutrients. "Microbes form the bulk ...

Shining light on neurodegenerative pathway

2013-09-18

University of Adelaide researchers have identified a likely molecular pathway that causes a group of untreatable neurodegenerative diseases, including Huntington's disease and Lou Gehrig's disease. The group of about 20 diseases, which show overlapping symptoms that typically include nerve cell death, share a similar genetic mutation mechanism ‒ but how this form of mutation causes these diseases has remained a mystery. "Despite the genes for some of these diseases having been identified 20 years ago, we still haven't understood the underlying mechanisms that ...

Novel treatment for gonorrhea acts like a 'live vaccine,' prevents reinfection, animal study shows

2013-09-18

BUFFALO, N.Y. -- A new gonorrhea treatment, based on an anti-cancer therapy developed by a Buffalo startup company, has successfully eliminated gonococcal infection from female mice and prevented reinfection, according to research published today by University at Buffalo scientists in the Journal of Infectious Diseases. Through TherapyX Inc., an early stage biotech company in Buffalo, the UB researchers have a $300,000 Small Business Innovation Research grant to develop the technology to treat and prevent gonorrhea infection. UB's Office for Science, Technology Transfer ...

Modeling and managing schizophrenia

2013-09-18

Schizophrenia is a potentially debilitating mental illness affecting a person's thought processes, perception, language and sense of oneself. Globally, 7 out of every 1000 are affected, accounting for 24 million patients. Significant risk factors for the illness in males is serious problems during birth or fetal hypoxia while increased cerebral ventricular size in both infancy and adulthood due to embryological defects can underlie the condition in other patients. However, it is a multifaceted illness that occurs through a combination of biological factors as well as socioeconomic ...

UCLA doctors successfully 'vacuum' 2-foot blood clot out of patient's heart

2013-09-18

Todd Dunlap, 62, arrived at Ronald Reagan UCLA Medical Center's emergency room on Aug. 8 suffering from shortness of breath, fatigue and extreme cold. When a CT scan revealed a 24-inch clot stretching from his legs into his heart, doctors feared the mass could break loose and lodge in his lungs, blocking oxygen and killing him instantly. Dr. John Moriarty gave his patient a choice. Dunlap could have open-heart surgery or undergo a new minimally invasive procedure using a device called AngioVac to vacuum the massive clot out of his heart. The catch? The procedure had ...

NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research

Research team uncovers root cause of multiple myeloma relapse

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: