Welcome!

Agile Computing Authors: Sanjay Zalavadia, Xenia von Wedel, Pat Romanski, Elizabeth White, Liz McMillan

News Feed Item

Gene sequencing project identifies abnormal gene that launches rare childhood leukemia

St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project discovery provides insight into a tough-to-cure form of acute myeloid leukemia that lays the groundwork for clinical care advances

MEMPHIS, Tenn., Nov. 12, 2012 /PRNewswire/ -- Research led by the St. Jude Children's Research Hospital – Washington University Pediatric Cancer Genome Project has identified a fusion gene responsible for almost 30 percent of a rare subtype of childhood leukemia with an extremely poor prognosis.

To view the multimedia assets associated with this release, please click: http://www.multivu.com/mnr/58586-st-jude-children-s-research-hospital-gene-sequencing-childhood-leukemia

The finding offers the first evidence of a mistake that gives rise to a significant percentage of acute megakaryoblastic leukemia (AMKL) cases in children. AMKL accounts for about 10 percent of pediatric acute myeloid leukemia (AML). The discovery paves the way for desperately needed treatment advances.

Investigators traced the genetic misstep to the rearrangement of chromosome 16, which brings together pieces of two genes and sets the stage for production of an abnormal protein. The fusion protein features the front end of CBFA2T3, a blood protein, and the back of GLIS2, a protein that is normally produced only in the kidney. Work that appears in the November 13 edition of the journal Cancer Cell reports that in a variety of laboratory models the CBFA2T3-GLIS2 protein switched on genes that drive immature blood cells to keep dividing long after normal cells had died. This alteration directly contributes to leukemia.

AMKL patients with the fusion gene were also found to be at high risk of failing therapy. Researchers checked long-term survival of 40 AMKL patients treated at multiple medical centers around the world and found about 28 percent of patients with the fusion gene became long-term survivors, compared to 42 percent for patients without CBFA2T3-GLIS2. Overall long-term survival for pediatric AML patients in the U.S. is now 71 percent.

"The discovery of the CBFA2T3-GLIS2 fusion gene in a subset of patients with AMKL paves the way for improved diagnostic testing, better risk stratification to help guide treatment and more effective therapeutic interventions for this aggressive childhood cancer," said James Downing, M.D., St. Jude scientific director and the paper's corresponding author. The first author is Tanja Gruber, M.D., Ph.D., an assistant member in the St. Jude Department of Oncology.

Co-author Richard Wilson, Ph.D., director of The Genome Institute at Washington University School of Medicine in St. Louis, noted: "We identified this unusual gene fusion by comparing the genome of children's healthy cells with the genome of their cancer cells. This type of in-depth exploration and analysis is crucial to finding unexpected structural rearrangements in the DNA that can lead to cancer. With this discovery, we now can search for more effective treatment options that target this precise defect."

The study is part of the Pediatric Cancer Genome Project, a three-year collaboration between St. Jude and Washington University to sequence the complete normal and cancer genomes of 600 children and adolescents with some of the most aggressive and least understood cancers. The human genome is the instruction book for assembling and sustaining a person. The instructions are packaged in the DNA molecule. Sequencing the genome involves determining the exact order of the four chemical bases that make up DNA. Human DNA is organized into 46 chromosomes.

"We focused on AMKL because no one had any idea of what caused this leukemia in most patients," Gruber said. The study excluded AMKL patients who were infants or children with Down syndrome because earlier research had linked their disease to other chromosomal rearrangements.

When researchers in this study sequenced just the genes that were switched on in the AMKL cells of 14 young patients, the scientists discovered half carried the CBFA2T3-GLIS2 fusion. Additional fusion genes were identified in five of the other patients. Each of those fusion genes occurred in a single patient. The genes involved included HOXA9 and MN1, both previously linked to leukemia, and GATA2 and FLII, which play roles in normal development of the megakaryocytic blood cells that are targeted in AMKL. Megakaryocytes produce the platelets that help blood clot.

Additional sequencing of DNA from adult and pediatric AMKL patients, including whole genome sequencing of the normal and cancer cells of four young AMKL patients, found the CBFA2T3-GLIS2 protein was unique to pediatric AMKL. Of the 48 pediatric AMKL patients screened in this study, 13 carried the fusion gene. None of 28 adult AMKL patients screened had the gene.

"Whole genome sequencing has allowed us to detect alterations in cancer cells that were previously unknown. Many of these changes contribute directly to the development of cancer," Gruber said. "Such sequencing also provides the deeper understanding of the disease that is critical for developing more effective, less-toxic targeted therapies."

GLIS2 is a transcription factor, meaning it attaches to DNA and turns genes on or off. GLIS2 is normally switched off in blood cells and has not been previously linked to cancer.

Working in several laboratory models, researchers showed that GLIS2, either alone or in the fusion gene, increased the activity of other genes in pathways that control cell functions disrupted in cancer. The genes include BMP2 and BMP4, which are now the focus of additional research. The genes are in a pathway that is active early in the developing blood system. This study implicated the genes in AMKL.

The study's other authors are Amanda Larson Gedman, Jinghui Zhang, Cary Koss, Suresh Marada, Shann-Ching Chen, Stacey Ogden, Jinjun Dang, Gang Wu, Stanley Pounds, Lei Shi, John Easton, Heather Mulder, Michael Rusch, Matthew Parker, Jing Ma, Sheila Shurtleff, Jeffrey Rubnitz and Ching-Hon Pui, all of St. Jude;  Huy Ta, Vedant Gupta, Anna Andersson, Michael Barbato, Jayanthi Manne, Jianmin Wang, Ramapriya Ganti and Ina Radtke, all formerly of St. Jude; Xiaoping Su, Steven Kornblau, Farhad Ravandi and Hagop Kantarjian, all of  MD Anderson Cancer Center, Houston; Swati Ranade, Pacific Biosciences, Menlo Park, Calif.; Li Ding, Timothy Ley and Elaine Mardis, all of Washington University; Giovanni Cazzaniga and Andrea Biondi, both of University of Milan-Bicocca, Monza, Italy; Stephen Nimer, Sloan-Kettering Institute, New York; Konstanze Dohner and Hartmut Dohner, both of University of Ulm, Germany; Paola Ballerini, Hospital Armand-Trousseau, Paris;  Daisuke Tomizawa, Tokyo Medical and Dental University; Souichi Adachi, Kyoto University, Japan; Yasuhide Hayashi, Gunma Children's Medical Center, Japan; Akio Tawa, Osaka National Hospital, Japan; Lee-Yung Shih, Chang Gung University, Taipei; and Der-Cherng Liang, Mackay Memorial Hospital, Taipei.

The research was funded in part by the Pediatric Cancer Genome Project, including Kay Jewelers, a lead project sponsor; the National Institutes of Health (P30CA021765); the Eric Trump Foundation; a Leukemia & Lymphoma Society Specialized Center of Research grant and ALSAC.

St. Jude Children's Research Hospital
Since opening 50 years ago, St. Jude Children's Research Hospital has played a pivotal role in pushing overall U.S. pediatric cancer survival rates from 20 to 80 percent. Founded by the late entertainer Danny Thomas, St. Jude is the first and only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. St. Jude is also a leader in research and treatment of life-threatening blood disorders and infectious diseases in children. No family ever pays St. Jude for the care their child receives. To learn more, visit www.stjude.org. Follow us on Twitter @StJudeResearch.

Washington University School of Medicine
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

SOURCE St. Jude Children's Research Hospital

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
Machine Learning helps make complex systems more efficient. By applying advanced Machine Learning techniques such as Cognitive Fingerprinting, wind project operators can utilize these tools to learn from collected data, detect regular patterns, and optimize their own operations. In his session at 18th Cloud Expo, Stuart Gillen, Director of Business Development at SparkCognition, discussed how research has demonstrated the value of Machine Learning in delivering next generation analytics to imp...
The cloud promises new levels of agility and cost-savings for Big Data, data warehousing and analytics. But it’s challenging to understand all the options – from IaaS and PaaS to newer services like HaaS (Hadoop as a Service) and BDaaS (Big Data as a Service). In her session at @BigDataExpo at @ThingsExpo, Hannah Smalltree, a director at Cazena, provided an educational overview of emerging “as-a-service” options for Big Data in the cloud. This is critical background for IT and data profession...
A strange thing is happening along the way to the Internet of Things, namely far too many devices to work with and manage. It has become clear that we'll need much higher efficiency user experiences that can allow us to more easily and scalably work with the thousands of devices that will soon be in each of our lives. Enter the conversational interface revolution, combining bots we can literally talk with, gesture to, and even direct with our thoughts, with embedded artificial intelligence, wh...
Whether your IoT service is connecting cars, homes, appliances, wearable, cameras or other devices, one question hangs in the balance – how do you actually make money from this service? The ability to turn your IoT service into profit requires the ability to create a monetization strategy that is flexible, scalable and working for you in real-time. It must be a transparent, smoothly implemented strategy that all stakeholders – from customers to the board – will be able to understand and comprehe...
When people aren’t talking about VMs and containers, they’re talking about serverless architecture. Serverless is about no maintenance. It means you are not worried about low-level infrastructural and operational details. An event-driven serverless platform is a great use case for IoT. In his session at @ThingsExpo, Animesh Singh, an STSM and Lead for IBM Cloud Platform and Infrastructure, will detail how to build a distributed serverless, polyglot, microservices framework using open source tec...
Connected devices and the industrial internet are growing exponentially every year with Cisco expecting 50 billion devices to be in operation by 2020. In this period of growth, location-based insights are becoming invaluable to many businesses as they adopt new connected technologies. Knowing when and where these devices connect from is critical for a number of scenarios in supply chain management, disaster management, emergency response, M2M, location marketing and more. In his session at @Th...
In his keynote at 18th Cloud Expo, Andrew Keys, Co-Founder of ConsenSys Enterprise, provided an overview of the evolution of the Internet and the Database and the future of their combination – the Blockchain. Andrew Keys is Co-Founder of ConsenSys Enterprise. He comes to ConsenSys Enterprise with capital markets, technology and entrepreneurial experience. Previously, he worked for UBS investment bank in equities analysis. Later, he was responsible for the creation and distribution of life sett...
Cloud Expo, Inc. has announced today that Andi Mann returns to 'DevOps at Cloud Expo 2016' as Conference Chair The @DevOpsSummit at Cloud Expo will take place on November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. "DevOps is set to be one of the most profound disruptions to hit IT in decades," said Andi Mann. "It is a natural extension of cloud computing, and I have seen both firsthand and in independent research the fantastic results DevOps delivers. So I am excited t...
"We work in the area of Big Data analytics and Big Data analytics is a very crowded space - you have Hadoop, ETL, warehousing, visualization and there's a lot of effort trying to get these tools to talk to each other," explained Mukund Deshpande, head of the Analytics practice at Accelerite, in this SYS-CON.tv interview at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
"delaPlex is a software development company. We do team-based outsourcing development," explained Mark Rivers, COO and Co-founder of delaPlex Software, in this SYS-CON.tv interview at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
IoT is rapidly changing the way enterprises are using data to improve business decision-making. In order to derive business value, organizations must unlock insights from the data gathered and then act on these. In their session at @ThingsExpo, Eric Hoffman, Vice President at EastBanc Technologies, and Peter Shashkin, Head of Development Department at EastBanc Technologies, discussed how one organization leveraged IoT, cloud technology and data analysis to improve customer experiences and effi...
Basho Technologies has announced the latest release of Basho Riak TS, version 1.3. Riak TS is an enterprise-grade NoSQL database optimized for Internet of Things (IoT). The open source version enables developers to download the software for free and use it in production as well as make contributions to the code and develop applications around Riak TS. Enhancements to Riak TS make it quick, easy and cost-effective to spin up an instance to test new ideas and build IoT applications. In addition to...
The idea of comparing data in motion (at the sensor level) to data at rest (in a Big Data server warehouse) with predictive analytics in the cloud is very appealing to the industrial IoT sector. The problem Big Data vendors have, however, is access to that data in motion at the sensor location. In his session at @ThingsExpo, Scott Allen, CMO of FreeWave, discussed how as IoT is increasingly adopted by industrial markets, there is going to be an increased demand for sensor data from the outermos...
CenturyLink has announced that application server solutions from GENBAND are now available as part of CenturyLink’s Networx contracts. The General Services Administration (GSA)’s Networx program includes the largest telecommunications contract vehicles ever awarded by the federal government. CenturyLink recently secured an extension through spring 2020 of its offerings available to federal government agencies via GSA’s Networx Universal and Enterprise contracts. GENBAND’s EXPERiUS™ Application...
The cloud market growth today is largely in public clouds. While there is a lot of spend in IT departments in virtualization, these aren’t yet translating into a true “cloud” experience within the enterprise. What is stopping the growth of the “private cloud” market? In his general session at 18th Cloud Expo, Nara Rajagopalan, CEO of Accelerite, explored the challenges in deploying, managing, and getting adoption for a private cloud within an enterprise. What are the key differences between wh...
Presidio has received the 2015 EMC Partner Services Quality Award from EMC Corporation for achieving outstanding service excellence and customer satisfaction as measured by the EMC Partner Services Quality (PSQ) program. Presidio was also honored as the 2015 EMC Americas Marketing Excellence Partner of the Year and 2015 Mid-Market East Partner of the Year. The EMC PSQ program is a project-specific survey program designed for partners with Service Partner designations to solicit customer feedbac...
The IoT is changing the way enterprises conduct business. In his session at @ThingsExpo, Eric Hoffman, Vice President at EastBanc Technologies, discussed how businesses can gain an edge over competitors by empowering consumers to take control through IoT. He cited examples such as a Washington, D.C.-based sports club that leveraged IoT and the cloud to develop a comprehensive booking system. He also highlighted how IoT can revitalize and restore outdated business models, making them profitable ...
There are several IoTs: the Industrial Internet, Consumer Wearables, Wearables and Healthcare, Supply Chains, and the movement toward Smart Grids, Cities, Regions, and Nations. There are competing communications standards every step of the way, a bewildering array of sensors and devices, and an entire world of competing data analytics platforms. To some this appears to be chaos. In this power panel at @ThingsExpo, moderated by Conference Chair Roger Strukhoff, Bradley Holt, Developer Advocate a...
SYS-CON Events has announced today that Roger Strukhoff has been named conference chair of Cloud Expo and @ThingsExpo 2016 Silicon Valley. The 19th Cloud Expo and 6th @ThingsExpo will take place on November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. "The Internet of Things brings trillions of dollars of opportunity to developers and enterprise IT, no matter how you measure it," stated Roger Strukhoff. "More importantly, it leverages the power of devices and the Interne...
In addition to all the benefits, IoT is also bringing new kind of customer experience challenges - cars that unlock themselves, thermostats turning houses into saunas and baby video monitors broadcasting over the internet. This list can only increase because while IoT services should be intuitive and simple to use, the delivery ecosystem is a myriad of potential problems as IoT explodes complexity. So finding a performance issue is like finding the proverbial needle in the haystack.