Discovery pinpoints cause of 2 types of leukemia

Results provide insights into possible new treatment approach with FDA-approved drugs

2013-05-10

(Press-News.org) PORTLAND, Ore. − Patients with two forms of leukemia, who currently have no viable treatment options, may benefit from existing drugs developed for different types of cancer, according to a study conducted by researchers at the Knight Cancer Institute at Oregon Health & Science University (OHSU).

The study, published in the May 9 edition of the New England Journal of Medicine, isolated the molecular mutation that causes chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) in some patients. That mutation, occurring in a gene called colony stimulating factor 3 receptor (CSF3R), initiates a chain reaction involving other gene families known as SRC, JAK, and TNK2, which subsequently drives these diseases.

This discovery is promising for patients as it will aid in diagnosing these cancers, which are currently difficult for physicians to distinguish from other leukemias. More importantly, the study results suggest that these patients could be helped by existing FDA-approved drugs designed to inhibit the chain reactions impacting JAK and SRC/TNK2, though clinical trials are needed.

"Our ability to rapidly pinpoint a new cancer-driving mutation demonstrates the power of integrating improved genome sequencing technology. It will accelerate our ability to tailor treatments to individuals and each research victory gives us more insight into the nature of this complex disease," said Jeffrey W. Tyner, Ph.D., an assistant professor with the OHSU Knight Cancer Institute and Cell & Developmental Biology Department, whose lab led the research. "What distinguished this research was our method for matching voluminous amounts of gene sequencing data with drug sensitivity data to quickly deduce which mutations were relevant in causing disease and this allows us to make a difference for patients who don't currently have good therapeutic options."

Tyner and the other researchers who conducted this study used a combination of tests not yet commonly deployed together for research on primary specimens collected from cancer patients. They performed gene sequencing on specimens from 27 patients, creating a profile of the possible genetic causes of these diseases. This enabled them to highlight the important mutations that were common among CNL and aCML patients. As they gathered information on potentially relevant mutations, they simultaneously tested how fresh samples of patients' cancer cells responded to different drugs. This enabled the scientists to link drug efficacy to CSF3R gene mutations.

The two-pronged study approach provided researchers with the ability to quickly home in on and verify a root cause of these rare forms of leukemia. Of the 27 patients in the study, 16, or about 59 percent, had the CSF3R mutation.

"This approach allows us to rapidly discover mutations that are fundamental to cancer growth and identify drugs that might be used to combat them," said Julia Maxson, Ph.D., of the OHSU Knight Cancer Institute, who was first author on the study. "Our findings are not only promising for the treatment of patients with CNL and aCML but also validate our approach to identify new drug targets in cancer."

In fact, during the study period, a CNL patient was treated with the FDA-approved drug ruxolitinib, which inhibits the cancer cell growth initiated by the CSF3R mutation. This treatment resulted in a dramatic improvement in the patient's condition.

CNL and aCML impact several hundred patients in the United States each year. Patients afflicted with these conditions typically live only two to three years. These forms of cancer have also been difficult to diagnose because there wasn't enough known about their genetic drivers. Knowing that they are defined by mutations in CSF3R provides physicians with a means to confirm a diagnosis. Tests for this mutation are already available; the OHSU Knight Diagnostic Laboratories' GeneTrails panel for leukemias has the capability to check for this mutation.

In an editorial that accompanies the study in the New England Journal of Medicine, Jerald Radich, M.D., of the Fred Hutchinson Cancer Research Center in Seattle, wrote that the approach is "an example of what genetically informed treatment may look like in the near future." Radich continued: "This is how we will beat cancer, one gene, one disease at a time."

### This study was funded by the Leukemia & Lymphoma Society, The V Foundation, William Lawrence & Blanche Hughes Foundation, Gabrielle's Angel Foundation and the Howard Hughes Medical Institute. Researchers who contributed are also supported by grants (including 5UL1RR024140, 1-K99-CA151670-01A1, 4 R00CA151457-03 and 5P30CA069533-13) offered through the National Institutes of Health, including the National Cancer Institute.

In in addition to Tyner and Maxson, contributors from OHSU: Angela G. Fleischman, M.D., Ph.D.; Anupriya Agarwal, Ph.D.; Christopher A. Eide, B.A.; Daniel Bottomly, M.S.; Beth Wilmot, Ph.D.; Shannon K. McWeeney, Ph.D.; Cristina E. Tognon, Ph.D.;; Bill H. Chang, M.D., Ph.D.; Marc M. Loriaux, M.D., Ph.D. and Brian J. Druker, M.D.

Other contributes are Jason Gotlib, M.D., of Stanford Cancer Institute, Stanford University School of Medicine; Daniel A. Pollyea, M.D., of the University of Colorado School of Medicine; J. Blake Pond, M.S., and Robert H. Collins, M.D., of the University of Texas Southwestern Medical Center; Basem Goueli, M.D., Ph.D., of St. Luke's Regional Cancer Center; Stephen T. Oh, M.D., Ph.D., of Washington University; and Michael W. Deininger, M.D., Ph.D., University of Utah.

ELSE PRESS RELEASES FROM THIS DATE:

Young women hold the key to success of 'sunless tanning' products, Baylor researcher finds

2013-05-10

Sunless tanning — whether with lotions, bronzers or tanning pills — has been promoted as an effective substitute to dodge the health risks of ultraviolet rays, but if the products don't provide the perfect tan, young women likely will not use them, according to a Baylor University researcher. "The feeling is 'I tan, I feel good, I'll look good tomorrow . . . What's health?'" said Jay Yoo, Ph.D., an assistant professor of family and consumer sciences in Baylor's College of Arts & Sciences. He conducted a study of 182 Caucasian female college students, with an average age ...

CU study suggests link between tumor suppressors and starvation survival

2013-05-10

A particular tumor suppressor gene that fights cancer cells does more than clamp down on unabated cell division -- the hallmark of the disease -- it also can help make cells more fit by allowing them to fend off stress, says a University of Colorado Boulder study. CU-Boulder Professor Min Han said the research team was interested in how a common tumor suppressor gene known as Retinoblastoma 1, or Rb, behaved under conditions of starvation. The question is important, said Han, because it may help researchers understand why many cancer cells are more susceptible to starvation ...

Scientists confirm that the Justinianic Plague was caused by the bacterium Yersinia pestis

2013-05-10

From the several pandemics generally called 'pestilences' three are historically recognized as due to plague, but only for the third pandemic of the 19th to 21st centuries AD there were microbiological evidences that the causing agent was the bacterium Yersinia pestis. "For a long time scholars from different disciplines have intensively discussed about the actual etiological agents of the past pandemics. Only ancient DNA analyses carried out on skeletal remains of plague victims could finally conclude the debate", said Dr. Barbara Bramanti of the Palaeogenetics Group at ...

Secret streets of Britain's Atlantis are revealed

2013-05-10

A University of Southampton professor has carried out the most detailed analysis ever of the archaeological remains of the lost medieval town of Dunwich, dubbed 'Britain's Atlantis'. Funded and supported by English Heritage, and using advanced underwater imaging techniques, the project led by Professor David Sear of Geography and Environment has produced the most accurate map to date of the town's streets, boundaries and major buildings, and revealed new ruins on the seabed. Professor Sear worked with a team from the University's GeoData Institute; the National Oceanography ...

The Elephant's Tomb in Carmona may have been a temple to the god Mithras

2013-05-10

The so-called Elephant's Tomb in the Roman necropolis of Carmona (Seville, Spain) was not always used for burials. The original structure of the building and a window through which the sun shines directly in the equinoxes suggest that it was a temple of Mithraism, an unofficial religion in the Roman Empire. The position of Taurus and Scorpio during the equinoxes gives force to the theory. The Carmona necropolis (Spain) is a collection of funeral structures from between the 1st century B.C. and the 2nd century A.D. One of these is known as the Elephant's Tomb because a ...

New magnetic graphene may revolutionize electronics

2013-05-10

Researchers from IMDEA-Nanociencia Institute and from Autonoma and Complutense Universities of Madrid (Spain) have managed to give graphene magnetic properties. The breakthrough, published in the journal 'Nature Physics', opens the door to the development of graphene-based spintronic devices, that is, devices based on the spin or rotation of the electron, and could transform the electronics industry. Scientists were already aware that graphene, an incredible material formed of a mesh of hexagonal carbon atoms, has extraordinary conductivity, mechanical and optical properties. ...

NRL shatters endurance record for small electric UAV

2013-05-10

WASHINGTON--Researchers at the U.S. Naval Research Laboratory flew their fuel cell powered Ion Tiger unmanned aerial vehicle (UAV) for 48 hours and 1 minute, April 16 to 18, by using liquid hydrogen (LH2) fuel in a new, NRL-developed, cryogenic fuel storage tank and delivery system. This flight shatters their previous record of 26 hours and 2 minutes set in 2009 using the same vehicle, but with gaseous hydrogen stored at 5,000 pounds per square inch (psi). Liquid hydrogen is three times denser than compressed hydrogen. The cryogenic liquid is stored in a lightweight tank, ...

Study finds gaps in 'decision aids' designed to help determine right cancer screening option

2013-05-10

ANN ARBOR, Mich. — When it comes to a cancer diagnosis, timing can be everything – the sooner it's found, the more treatable it is. But when and how often should someone get screened? A growing number of educational, interactive tools known as "decision aids" – such as videodiscs, audiotapes, workbooks and pamphlets – are intended to supplement patient-doctor discussions on the pros and cons of timing, methods and frequency for different types of cancer screening. A University of Michigan study found that despite strong recommendations from the medical community ...

Revealing hidden fungal species using DNA: The importance of recognizing cryptic diversity

2013-05-10

Our ability to assess biological diversity, ecosystem health, ecological interactions, and a wide range of other important processes is largely dependent on accurately recognizing species. However, identifying and describing species is not always a straightforward task. In some cases, a single species may show a high level of morphological variation, while in other cases, multiple morphologically similar species may be hidden under a single species name. Cryptic species, two or more distinct species that are erroneously classified under a single species name, are found ...

Baylor University researcher finds earliest evidence of human ancestors hunting & scavenging

2013-05-10

WACO, Texas (May 9, 2013) -- A recent Baylor University research study has shed new light on the diet and food acquisition strategies of some the earliest human ancestors in Africa. Beginning around two million years ago, early stone tool-making humans, known scientifically as Oldowan hominin, started to exhibit a number of physiological and ecological adaptations that required greater daily energy expenditures, including an increase in brain and body size, heavier investment in their offspring and significant home-range expansion. Demonstrating how these early humans ...

Discovery pinpoints cause of 2 types of leukemia

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: