Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers discover how a mutated protein outwits evolution and fuels leukemia

Findings suggest a potent new therapeutic target for certain types of cancer

Scientists have discovered the survival secret to a genetic mutation that stokes leukemia cells, solving an evolutionary riddle and paving the way to a highly targeted therapy for leukemia.

In a paper published today in Cell, researchers at NYU Langone Medical Center describe how a mutated protein, called Fbxw7, behaves differently when expressed in cancer cells versus healthy cells. "Fbxw7 is essential for making blood cells, so the big mystery is why a mutation on a gene so important for survival would persist," says lead author Iannis Aifantis, PhD, chair of pathology at NYU Langone Medical Center and an Early Career Scientist at Howard Hughes Medical Institute. "What we've found is that the mutation affects cancerous cells but not healthy cells."

The Fbxw7 protein regulates the production of so-called hematopoietic stem cells, precursors that give rise to all types of blood cells. Without Fbxw7, the body loses the ability to produce blood and eventually succumbs to anemia. Scientists are only beginning to understand why mutated Fbxw7 appears in a significant portion of human tumors, including gastric, prostate, and some breast cancers. The mutation is especially prevalent in T-cell acute lymphoblastic leukemia, or T-ALL, a rare but lethal type of pediatric leukemia that causes the over-production of immature white blood cells.

In their experiments, Dr. Aifantis, working in collaboration with graduate student Bryan King and others, began by introducing mutated Fbxw7 into healthy blood stem cells in mice. "We thought the mutation would induce anemia, just as it does when Fbxw7 is deleted," says Dr. Aifantis. But to the researchers' surprise, nothing happened—the stem cells continued to manufacture blood cells.

When the researchers then introduced in mice the mutated Fbxw7 into leukemic blood stem cells—those that overproduce white blood cells and cause leukemia—the cancer accelerated. "We found that the mutation made leukemia stem cells much more aggressive," Dr. Aifantis says.

In follow-up experiments, the researchers showed that Fbxw7 binds to and degrades a protein called Myc, which fuels leukemic stem cells, and has long been associated with many other cancers and the recurrence of cancer after treatment. When Fbxw7 is mutated, Myc is left unchecked, they found, and the population of cancer stem cells swells. This insight also helps explain why healthy blood stem cells seem to "ignore" mutated Fbxw7. Unlike leukemic stem cells, healthy blood stem cells typically lie dormant until the body requires an emergency supply of blood and they rarely express Myc. "Normal blood stem cells express very little Myc because they are not cycling. A mutation does not affect the substrate because the substrate does not exist," says Dr. Aifantis. "Leukemia stem cells, however, do express Myc and Fbxw7 mutations increase its abundance."

The researchers then wondered if eliminating Myc could potentially block leukemia. Indeed, deleting the Myc gene in mice with leukemia depleted leukemic stem cells and stopped the growth of tumors. They achieved the same results in mice and human cell and bone marrow samples of T-ALL using a new class of cancer drug called a BET inhibitor that blocks Myc. "We found that the BET inhibitor could actually kill leukemia stem cells. And without stem cells, the leukemia simply cannot grow," says Dr. Aifantis.

The researchers believe they can use the BET inhibitor to target pediatric and adult T-ALL leukemia. This work was supported by a grant from the National Cancer Institute.

About NYU Langone Medical Center

NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one of the nation's premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of four hospitals – Tisch Hospital, its flagship acute care facility; the Hospital for Joint Diseases, recognized as one of the nation's leading hospitals dedicated to orthopaedics and rheumatology; Hassenfeld Pediatric Center, a comprehensive pediatric hospital supporting a full array of children's health services; and Rusk Rehabilitation, inpatient and outpatient therapy services devoted entirely to rehabilitation medicine – plus NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center's tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research. For more information, go to

Christopher Rucas | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>