Welcome!

Agile Computing Authors: Yeshim Deniz, Pat Romanski, Liz McMillan, Ed Featherston, Elizabeth White

News Feed Item

Study Involving Twin Sisters Provides Clues for Battling Aggressive Cancers

CINCINNATI, Feb. 9, 2014 /PRNewswire-USNewswire/ -- Analyzing the genomes of twin 3-year-old sisters – one healthy and one with aggressive leukemia – led an international team of researchers to identify a novel molecular target that could become a way to treat recurring and deadly malignancies.

(Logo: http://photos.prnewswire.com/prnh/20110406/MM79025LOGO)

Scientists in China and the United States report their findings online Feb. 9 in Nature Genetics. The study points to a molecular pathway involving a gene called SETD2, which can mutate in blood cells during a critical step as DNA is being transcribed and replicated.

The findings stem from the uniquely rare opportunity to compare the whole genomes of the monozygotic twin sisters (which means they came from a single egg). This led to a series of follow up experiments in human samples from leukemia patients and mouse models of human disease. Those tests verified and extended initial findings researchers gleaned from the twin sisters' blood samples, according to Gang Huang, PhD, co-corresponding author and a researcher in the divisions of Pathology and Experimental Hematology and Cancer Biology at Cincinnati Children's Hospital Medical Center.

"We reasoned that monozygotic twins discordant for human leukemia would have identical inherited genetic backgrounds and well-matched tissue-specific events," Huang said. "This provided a strong basis for comparison and analysis. We identified a gene mutation involving SETD2 that contributes to the initiation and progression of leukemia by promoting the self-renewal potential of leukemia stem cells."

The twin sisters' genomes were compared at the laboratory of co-corresponding author Qian-fei Wang, PhD, Beijing Institute of Genomics, Chinese Academy of Sciences in Beijing, China. The sick sister had a particularly acute and aggressive form of the acute myeloid leukemia (AML) known as MLL, or multi-lineage leukemia.

Acute and aggressive leukemia like MLL develops and progresses rapidly in patients, requiring prompt treatment with chemotherapy, radiation or bone marrow transplant. These treatments can be risky or only partially effective. About 70 percent of people with AML respond initially to standard chemotherapy. Unfortunately, five-year survival rates vary between 15-70 percent, depending on the subtype of AML.

The researchers – including co-corresponding author Tao Cheng, MD, Chinese Academy of Medical Sciences & Peking Union Medical College in Tianjin, China – are searching for improved and more targeted treatment strategies. The authors show in their current study that the onset of aggressive and acute leukemia is fueled by a spiraling cascade of multiple gene mutations and what are called chromosomal translocations – essentially incorrect alignments of DNA and genetic information during cell replication.

In comparing the blood cells of both twin sisters, these researchers identified a chromosomal translocation generated what is known as the MLL-NRIP3 fusion leukemia gene. When they activated the MLL-NRIP3 gene in laboratory mouse models, the animals developed the same type of leukemia, but it took a long period of time for them to do so. Researchers said this suggested that there had to be additional cooperative epigenetic and molecular events in play to induce full-blown leukemia.

The authors went on to demonstrate that activation of the MLL-NRIP3 fusion leukemia gene cooperated with the molecular cascade (including mutations in SETD2) to cause the multi-lineage form of acute myeloid leukemia (AML). The scientists' initial clue came by looking for additional genomic alterations in the leukemic blood cells of the sick twin sister. They discovered activation of the MLL-NRIP3 fusion leukemia started the molecular cascade that led to bi-allelic (two mutations) in the gene SETD2 – a tumor suppressor and enzyme that regulates a specific histone modification protein called H3K36me3.

During a process called transcriptional elongation, SETD2 and H3K36me3 normally mark the zone for accurate gene transcription along the DNA. In the case of the sick twin sister, the gene mutations and molecular cascade disrupted the H3K36me3 mark, leading to abnormal transcription and the multi-lineage form of acute leukemia.

Researchers then analyzed blood samples from 241 people who had different forms acute leukemia. SETD2 mutations were found in samples from 6.2 percent of those patients. Patients with SETD2 mutations also had a leukemia associated with major chromosomal translocations and disruption of the H3K36me3 mark.  

In follow up tests on cell cultures of pre-leukemic cells and mouse models, researchers saw the same progression of gene mutations and related molecular events fuel the growth of leukemic cells. Researchers also noticed mutation of SETD2 activated two genes (MTOR and JAK-STAT) that known contributors to cancer and leukemia. The scientists decided to test two existing targeted molecular inhibitors of MTOR on pre-leukemic cells that are generated by SETD2 gene mutations.

That treatment resulted in a marked decrease in cell growth, indicating that SETD2 mutations activate numerous molecular pathways to generate leukemia. Huang said the tests also demonstrate that there are multiple opportunities to find new molecular targets for developing more effective drugs – in particular those that would target the MLL fusion-SETD2-H3K36me3 pathway for treating acute and aggressive multi-lineage leukemia.

Researchers are following up their current study by identifying additional pathways activated by mutations of SETD2. They also are looking possible new molecular targets and therapeutic strategies for block disruptions in the MLL fusions-SETD2-H3K36me3 pathway.

Other collaborating institutions include: the Institute of Hematology and Blood Diseases Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College; the University of Science & Technology, Wuhan, Hubei, China; Changhai Hospital, Second Military Medical University, Shanghai, China; the University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago Research Center, Chicago. Co-first authors are: Xiaofan Zhu, Fuhong He, Huimin Zeng, Shaoping Ling and Aili Chen.

Funding support came from: the China Ministry of Science and Technology (2011CB964801, 2012CB966600, 2010DFB30270); the Chinese Academy of Sciences; the National Natural Science Foundation of China (81090411, 81000220, 81130074, 30825017) Tianjin Municipal Science & Technology Commission (09ZCZDSF03800).

About Cincinnati Children's:
Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2013 Best Children's Hospitals ranking. It is ranked #1 for cancer and in the top 10 for nine of 10 pediatric specialties. Cincinnati Children's, a non-profit organization, is one of the top three recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at www.cincinnatichildrens.org. Connect on the Cincinnati Children's blog, via Facebook and on Twitter.

SOURCE Cincinnati Children's Hospital Medical Center

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

@ThingsExpo Stories
It is of utmost importance for the future success of WebRTC to ensure that interoperability is operational between web browsers and any WebRTC-compliant client. To be guaranteed as operational and effective, interoperability must be tested extensively by establishing WebRTC data and media connections between different web browsers running on different devices and operating systems. In his session at WebRTC Summit at @ThingsExpo, Dr. Alex Gouaillard, CEO and Founder of CoSMo Software, presented ...
Most people haven’t heard the word, “gamification,” even though they probably, and perhaps unwittingly, participate in it every day. Gamification is “the process of adding games or game-like elements to something (as a task) so as to encourage participation.” Further, gamification is about bringing game mechanics – rules, constructs, processes, and methods – into the real world in an effort to engage people. In his session at @ThingsExpo, Robert Endo, owner and engagement manager of Intrepid D...
Recently, WebRTC has a lot of eyes from market. The use cases of WebRTC are expanding - video chat, online education, online health care etc. Not only for human-to-human communication, but also IoT use cases such as machine to human use cases can be seen recently. One of the typical use-case is remote camera monitoring. With WebRTC, people can have interoperability and flexibility for deploying monitoring service. However, the benefit of WebRTC for IoT is not only its convenience and interopera...
Michael Maximilien, better known as max or Dr. Max, is a computer scientist with IBM. At IBM Research Triangle Park, he was a principal engineer for the worldwide industry point-of-sale standard: JavaPOS. At IBM Research, some highlights include pioneering research on semantic Web services, mashups, and cloud computing, and platform-as-a-service. He joined the IBM Cloud Labs in 2014 and works closely with Pivotal Inc., to help make the Cloud Found the best PaaS.
Everything run by electricity will eventually be connected to the Internet. Get ahead of the Internet of Things revolution. In his session at @ThingsExpo, Akvelon expert and IoT industry leader Sergey Grebnov provided an educational dive into the world of managing your home, workplace and all the devices they contain with the power of machine-based AI and intelligent Bot services for a completely streamlined experience.
Cloud-enabled transformation has evolved from cost saving measure to business innovation strategy -- one that combines the cloud with cognitive capabilities to drive market disruption. Learn how you can achieve the insight and agility you need to gain a competitive advantage. Industry-acclaimed CTO and cloud expert, Shankar Kalyana presents. Only the most exceptional IBMers are appointed with the rare distinction of IBM Fellow, the highest technical honor in the company. Shankar has also receive...
Business professionals no longer wonder if they'll migrate to the cloud; it's now a matter of when. The cloud environment has proved to be a major force in transitioning to an agile business model that enables quick decisions and fast implementation that solidify customer relationships. And when the cloud is combined with the power of cognitive computing, it drives innovation and transformation that achieves astounding competitive advantage.
Personalization has long been the holy grail of marketing. Simply stated, communicate the most relevant offer to the right person and you will increase sales. To achieve this, you must understand the individual. Consequently, digital marketers developed many ways to gather and leverage customer information to deliver targeted experiences. In his session at @ThingsExpo, Lou Casal, Founder and Principal Consultant at Practicala, discussed how the Internet of Things (IoT) has accelerated our abilit...
In his session at Cloud Expo, Alan Winters, U.S. Head of Business Development at MobiDev, presented a success story of an entrepreneur who has both suffered through and benefited from offshore development across multiple businesses: The smart choice, or how to select the right offshore development partner Warning signs, or how to minimize chances of making the wrong choice Collaboration, or how to establish the most effective work processes Budget control, or how to maximize project result...
To get the most out of their data, successful companies are not focusing on queries and data lakes, they are actively integrating analytics into their operations with a data-first application development approach. Real-time adjustments to improve revenues, reduce costs, or mitigate risk rely on applications that minimize latency on a variety of data sources. In his session at @BigDataExpo, Jack Norris, Senior Vice President, Data and Applications at MapR Technologies, reviewed best practices to ...
Data is the fuel that drives the machine learning algorithmic engines and ultimately provides the business value. In his session at Cloud Expo, Ed Featherston, a director and senior enterprise architect at Collaborative Consulting, discussed the key considerations around quality, volume, timeliness, and pedigree that must be dealt with in order to properly fuel that engine.
In his keynote at 19th Cloud Expo, Sheng Liang, co-founder and CEO of Rancher Labs, discussed the technological advances and new business opportunities created by the rapid adoption of containers. With the success of Amazon Web Services (AWS) and various open source technologies used to build private clouds, cloud computing has become an essential component of IT strategy. However, users continue to face challenges in implementing clouds, as older technologies evolve and newer ones like Docker c...
"Akvelon is a software development company and we also provide consultancy services to folks who are looking to scale or accelerate their engineering roadmaps," explained Jeremiah Mothersell, Marketing Manager at Akvelon, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
Two weeks ago (November 3-5), I attended the Cloud Expo Silicon Valley as a speaker, where I presented on the security and privacy due diligence requirements for cloud solutions. Cloud security is a topical issue for every CIO, CISO, and technology buyer. Decision-makers are always looking for insights on how to mitigate the security risks of implementing and using cloud solutions. Based on the presentation topics covered at the conference, as well as the general discussions heard between sessio...
To Really Work for Enterprises, MultiCloud Adoption Requires Far Better and Inclusive Cloud Monitoring and Cost Management … But How? Overwhelmingly, even as enterprises have adopted cloud computing and are expanding to multi-cloud computing, IT leaders remain concerned about how to monitor, manage and control costs across hybrid and multi-cloud deployments. It’s clear that traditional IT monitoring and management approaches, designed after all for on-premises data centers, are falling short in ...
Organizations planning enterprise data center consolidation and modernization projects are faced with a challenging, costly reality. Requirements to deploy modern, cloud-native applications simultaneously with traditional client/server applications are almost impossible to achieve with hardware-centric enterprise infrastructure. Compute and network infrastructure are fast moving down a software-defined path, but storage has been a laggard. Until now.
DXWorldEXPO LLC announced today that the upcoming DXWorldEXPO | CloudEXPO New York event will feature 10 companies from Poland to participate at the "Poland Digital Transformation Pavilion" on November 12-13, 2018.
Digital Transformation is much more than a buzzword. The radical shift to digital mechanisms for almost every process is evident across all industries and verticals. This is often especially true in financial services, where the legacy environment is many times unable to keep up with the rapidly shifting demands of the consumer. The constant pressure to provide complete, omnichannel delivery of customer-facing solutions to meet both regulatory and customer demands is putting enormous pressure on...
The best way to leverage your CloudEXPO | DXWorldEXPO presence as a sponsor and exhibitor is to plan your news announcements around our events. The press covering CloudEXPO | DXWorldEXPO will have access to these releases and will amplify your news announcements. More than two dozen Cloud companies either set deals at our shows or have announced their mergers and acquisitions at CloudEXPO. Product announcements during our show provide your company with the most reach through our targeted audienc...
In an era of historic innovation fueled by unprecedented access to data and technology, the low cost and risk of entering new markets has leveled the playing field for business. Today, any ambitious innovator can easily introduce a new application or product that can reinvent business models and transform the client experience. In their Day 2 Keynote at 19th Cloud Expo, Mercer Rowe, IBM Vice President of Strategic Alliances, and Raejeanne Skillern, Intel Vice President of Data Center Group and ...